Acetazolamide (Diamox) is used to treat glaucoma, edema due to drugs or heart failure, seizures and prevention and treatment of high altitude sickness.

It is also used as a respiratory stimulant in stable COPD patients who are hypercapnic and in the treatment of metabolic alkalosis.

Acetazolamide use in migraine Aura status:

• Up to 30% of the patients with migraine have associated aura prior to the episode.
• The aura is manifested by visual disturbances, enlarging scotomas, motor or sensory dysphasia, altered sensations, and tinnitus.
• Migraine aura status occurs when the patients have frequent or consecutive auras without headache.
• Migraine status aura is, although not associated with headache, is bothersome.
• Acetazolamide has been observed to be effective in patients with migraine aura status.
• It has also been found in case reports to be effective in patients with CADASIL (Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) manifesting as migraine with aura.
• Acetazolamide, however, has not been found to be effective for the prophylaxis of migraine or to abort the attack of migraine like the triptans (Sumatriptan and zolmitriptan)

Acetazolamide for hereditary paroxysmal ataxia:

• Patients of hereditary paroxysmal ataxia presenting with ataxia, dysarthria, and nystagmus were effectively treated with acetazolamide.

Acetazolamide for sleep apnea:

• Since acetazolamide makes the plasma PH acidic, it stimulates the respiratory center.
• Patients with central sleep apnea, chronic obstructive airway disease, and those with obesity hypoventilation syndrome may notice an improvement in the symptoms as a result of respiratory center stimulation.
• One study found a 69% reduction in the episodes of sleep apnea with Diamox therapy.

Acetazolamide in patients with hydrocephalus:

• Studies in animals have found the drug effective for the treatment of hydrocephalus.
• Animal studies have shown that it reduces ventricular pressure by reducing the production of CSF.
• However, its efficacy in humans is doubtful. The therapeutic effect of diamox in children was found to be negligible in one study.
• In adults, acetazolamide has some role in patients with idiopathic intracranial hypertension (pseudotumor cerebri).

Acetazolamide for Altitude sickness:

Diamox 250 mg and 500 mg tablets:

• Immediate-release tablets: 500-1000 mg/day in two to three divided doses.
• Extended-release capsules: 500 - 1000 mg/day once daily or in two divided doses.

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Acetazolamide for the Prevention of altitude sickness: 

Diamox 125 mg tablets:

• 125 mg twelve hourly
• Start taking acetazolamide one day before or at least on the day of ascent.
• Discontinue acetazolamide after staying at the same elevation for 2 to 3 days.

Note: 

• In situations of rapid ascent, 1000 mg per day is recommended along with dexamethasone.
• Dexamethasone should also be given to patients who develop cerebral edema.

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Acetazolamide dose for the treatment of Edema: 

• Oral and intravenous: 250-375 mg once daily

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Acetazolamide dose in seizures and epilepsy: 

• Oral: 8-30 mg/kg/day in divided doses.
• Maximum dose: 30 mg/kg/day or 1 g/day.

Note: 

• Minimal additional benefit with doses >16 mg/kg/day.
• The extended-release capsule is not recommended for the treatment of epilepsy.

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Acetazolamide dose in Glaucoma: 

• Chronic simple (open-angle):

  • Diamox 250 mg tablets 1-4 times/day or Diamox 500 mg extended-release capsule twice daily

• Secondary or acute (closed-angle): 

  • Initial dose:

    • 250-500 mg

  • maintenance dose:

    • 125-250 mg every 4 hours (250 mg every 12 hours has been effective in the short-term treatment of some patients)

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Metabolic alkalosis: 

• Diamox 500 mg tablets intravenously as a single dose

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Acetazolamide dose as a respiratory stimulant in stable hypercapnic COPD: 

• Diamox 250 mg tablets orally twice daily.

Acetazolamide dose in Children:

Diamox dosage for altitude sickness prophylaxis:

2.5 mg/kg/dose every 12 hours.

• Start taking the drug a day before or at least on the day of ascent and continue taking it for 3 days after stating at the same elevation

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Diamox altitude sickness pediatric dose (Treatment dose):

2.5 mg/kg/dose every 8-12 hours to a maximum dose of 250 mg/dose. 

Pregnancy Risk Factor C 

• Teratogenic effects have been shown in animal studies. Therefore, it is not recommended for pregnant women.
• Acetazolamide is found in breast milk. It is not recommended during lactation.

Diamox dose in kidney failure:

• Acetazolamide is contraindicated in marked renal impairment, however, the cutoff creatinine clearance has not been defined.

Cl cr 10-50 mL/minute:

• Administer it every 12 hours.

Cl cr <10 mL/minute:

• Avoid its use.

Hemodialysis:

• Moderately dialyzable (20% to 50%).

Diamox Dose in Liver disease:

• It is contraindicated in patients with cirrhosis or marked liver disease or dysfunction. 

Acetazolamide Side effects:

• Ophthalmologic:

  • Anaphylaxis,
  • blepharoconjunctivitis,
  • burning,
  • corneal disorders,
  • dry eyes,
  • erythema,
  • itching,
  • ocular stinging,
  • pain at the injection site.

• Neurologic side effects:

  • Flushing,
  • ataxia,
  • confusion,
  • convulsions,
  • depression,
  • dizziness,
  • drowsiness,
  • excitement,
  • fatigue,
  • fever,
  • headache,
  • malaise

• Dermatologic:

  • Allergic skin reactions,
  • photosensitivity,
  • Stevens-Johnson syndrome,
  • toxic epidermal necrolysis,
  • urticaria

• Endocrine & metabolic:

  • Electrolyte imbalance,
  • growth retardation (children),
  • hyperglycemia,
  • hypoglycemia,
  • hypokalemia,
  • hyponatremia,
  • metabolic acidosis

• Gastrointestinal adverse effects:

  • Appetite decreased,
  • diarrhea,
  • melena,
  • nausea,
  • taste alteration,
  • vomiting

• Genitourinary effects:

  • Crystalluria,
  • glycosuria,
  • hematuria,
  • polyuria,
  • renal failure

• Hematologic effects:

  • Agranulocytosis,
  • aplastic anemia,
  • leukopenia,
  • thrombocytopenia,
  • thrombocytopenic purpura

• Hepatic adverse effects:

  • Cholestatic jaundice,
  • fulminant hepatic necrosis,
  • hepatic insufficiency,
  • Abnormal liver function tests

• Neuromuscular & skeletal:

  • Flaccid paralysis,
  • paresthesia

• Ear problems:

  • Hearing disturbance,
  • tinnitus

• Miscellaneous:

  • Anaphylaxis

 Acetazolamide Contraindications: 

It should be avoided in the following patients:

• Severe allergic reactions to acetazolamide and/ or sulfonamides,
• Advanced liver disease
• Advanced kidney disease,
• Severe hyponatremia,
• Hypokalemia,
• Adrenal insufficiency, and
• Long-term use in noncongestive angle-closure glaucoma

Monitor:

• Monitor fluid & electrolytes,
• Liver function tests and
• Renal functions.

How to take Acetazolamide?

• Oral formulations of acetazolamide may be administered with food.
• It may cause an alteration in the taste, especially carbonated beverages.
• To avoid its bitter taste, crush the short-acting tablets and mix it with 10 ml of hot water and 10 ml of honey or chocolate syrup, but do not mix it with fruit juices.

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Intramuscular administration is not recommended because of severe pain.

Acetazolamide is compatible when mixed with almost any kind of intravenous fluid solution.

Acetazolamide Mechanism of Action:

• Acetazolamide blocks the enzyme carbonic acide reversibly, resulting in the excretion sodium, potassium and bicarbonate.
• It decreases the production aqueous humor, inhibits carbonic acidase in central nervous system, and retards abnormal and excessive discharges from CNS neuron.

The onset of action:

• 2 hours for oral formulations and 5 to 10 minutes for the intravenous formulation

Time to peak concentration in the plasma:

• Capsule (extended-release): 3-6 hours; Tablet: 1-4 hours

Excretion of acetazolamide:

• Urine (70% to 100% as unchanged drug).

International Brands:

• Acetadiazol
• Acetak
• Albox
• Apo-Acetazolamide
• Azol
• Carbinib
• Cetamid
• Diacarb
• Diamox
• Diamox Sustets
• Diazomid
• Diluran
• Diural
• Diuramid
• Evamox
• Fonurit
• Glaucomed
• Glaumox
• Glaupax
• Glauseta
• Huma-Zolamide
• Ledamox
• Medene
• Oculten
• Odemin
• Renamid
• Stazol
• Synomax
• Uramox
• Zolmide

Acetazolamide brands in Pakistan:

Acemox (Vega pharmaceruticalsLTD)

Tablets: 250mg:

30 tablets pack:Rs.30

AZM (Ethical laboratories (PVT) LTD)

Tablets: 250mg:

30 tablets pack:Rs.34

Diamox (Pfizer laboratories LTD)

Tablets: 250mg:

30 tabletspack:Rs.34.43

Evamox (Don valley pharmaceuticals (PVT) LTD)

Tablets: 250mg:

30 tablets pack:Rs.27

Setacar (Remington pharmaceuticals industries (PVT) LTD)

  Tablets: 250mg:

30 tablets pack:Rs.33.48