Health Canada has reviewed the potential risks of choroidal effusion (CE), acute myopia (AM), and acute angle-closure glaucoma (AACG) with the use of certain diuretics, including hydrochlorothiazide, chlorthalidone, indapamide, and acetazolamide. Health Canada has concluded that there is a link between the use of these medications and the risks of CE with AM or with AACG or with both AM and AACG; Health Canada's review also concluded that there might be a link between metolazone and the risk of these ophthalmic disorders. Health Canada is working with manufacturers to update the Canadian product safety information for these products to add a warning about these risks.
Further information may be found at https://hpr-rps.hres.ca/reg-content/summary-safety-review-detail.php?lang=en&linkID=SSR00261.
Metabolic alkalosis: Limited data available; dosing regimens variable: PMA ≥30 weeks: IV, Oral: 3 to 5 mg/kg/dose every 6 to 8 hours, commonly reported duration is 3 to 4 doses; most experience in patients with a PMA ≥40 weeks using IV administration, dosing shown to significantly lower serum bicarbonate concentrations (Andrews 2013; Tam 2014); another trial used 5 mg/kg/dose once daily for 3 doses with success in postcardiac surgery patients (age range: 8 days to 20 months) (Moffett 2007)
Altitude illness, acute:
Prevention: Limited data available: Infants, Children, and Adolescents: Oral: Immediate release: 2.5 mg/kg/dose every 12 hours started either the day before (preferred) or on the day of ascent and may be discontinued after staying at the same elevation for 2 to 3 days or if descent initiated; maximum dose: 125 mg/dose (Luks 2010). Note: The International Society for Mountain Medicine does not recommend prophylaxis in children except in the rare circumstance of unavoidable rapid ascent or in children with known previous susceptibility to acute mountain sickness (Pollard 2001). Higher doses are effective up to 500 mg, but are also associated with increased adverse effects and not recommended (Luks 2010).
Treatment: Acute mountain sickness (AMS); moderate: Limited data available: Infants, Children, and Adolescents: Oral: Immediate release: 2.5 mg/kg/dose every 8 to 12 hours; maximum dose: 250 mg/dose. Note: With high altitude cerebral edema, dexamethasone is the primary treatment; however, acetazolamide may be used adjunctively with the same treatment dose (Luks 2010; Pollard 2001).
Glaucoma:
Children <12 years: Limited data available: Oral: Immediate release: 10 to 30 mg/kg/day divided every 6 to 8 hours; maximum daily dose: 1,000 mg/day (Portellos 1998; Sabri 2006).
Children ≥12 years and Adolescents: Oral:
Immediate release: Limited data available: 15 to 30 mg/kg/day in divided doses every 6 to 8 hours; maximum daily dose: 1,000 mg/day.
Extended release (Diamox sequels):
Manufacturer's labeling: 500 mg twice daily.
Alternate dosing: Weight-directed dosing: Limited data available: 15 to 30 mg/kg/day in divided doses twice daily; maximum daily dose: 1,000 mg/day (Pagliaro 2002; Sabri 2006).
Edema: Limited data available: Infants, Children, and Adolescents: Oral (immediate release), IV: 5 mg/kg/dose once daily or every other day in the morning (Park 2014).
Epilepsy, short-term management: Limited data available: Infants, Children, and Adolescents: Oral: Immediate release: Usual range: 4 to 16 mg/kg/day in 3 to 4 divided doses; may titrate; maximum daily dose: 30 mg/kg/day or 1,000 mg/day (whichever is less) (Reiss 1996); Note: Minimal additional benefit with doses >16 mg/kg/day.
Metabolic alkalosis: Limited data available; dosing regimens variable: Infants, Children, and Adolescents: IV, Oral (immediate release): 5 mg/kg/dose once daily for 3 doses been used in a prospective trial of postcardiac surgical patients (age range: 8 days to 20 months) and results showed a significant decrease in serum bicarbonate concentrations (Moffett 2007). A retrospective trial of 34 pediatric patients (mean age: 1.9 years; range: 18 days to 12 years) reported a mean effective dose of 5.4 mg/kg/dose every 6 to 8 hours; a trend showed every 6-hour dosing had a higher success rate but not statistically significant (Andrews 2013). In adults, the reported dosing is 500 mg as a single dose (Marik 1991; Moviat 2006).
Pseudotumor cerebri: Limited data available:
Children: Oral: Immediate release: Usual reported initial dose: 15 to 25 mg/kg/day in 2 to 3 divided doses; may increase if needed to a maximum daily dose: 100 mg/kg/day or 2,000 mg/day (whichever is less); therapy continued until resolution of headache, disc swelling, and visual field abnormalities; usually several months (eg, 3 to 9 months) (Distelmaier 2006; Hacifazlioglu 2012; Ko 2010; Per 2013; Rangwala 2007; Soler 1998; Spennato 2011; Standridge 2010).
Adolescents: Oral: Immediate release: Initial: 500 mg twice daily; may increase if needed; maximum daily dose: 4,000 mg/day; usual adult dose range: 1,000 to 4,000 mg/day in 2 to 4 divided doses (Phillips 2012; Standridge 2010).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling; acetazolamide is contraindicated in severe renal impairment.
All patients: There are no dosage adjustments provided in the manufacturer's labeling; however, acetazolamide is contraindicated in patients with cirrhosis or severe liver impairment.
(For additional information see "Acetazolamide: Drug information")
Note: Doses below refer to the IR formulation unless otherwise specified.
Acute mountain sickness/high-altitude cerebral edema:
Prevention, moderate- to high-risk situations:
Note: Use in addition to gradual ascent; start the day before (preferred) or on the day of ascent (WMS [Luks 2019]).
Oral: 125 mg twice daily; may be discontinued after staying at the same elevation for 2 to 4 days or if descent is initiated (WMS [Luks 2019]).
Treatment:
Acute mountain sickness:
Note: For moderate to severe acute mountain sickness, some experts prefer dexamethasone or use acetazolamide as an adjunct to dexamethasone (Gallagher 2021; WMS [Luks 2019]).
Oral: 250 mg twice daily (WMS [Luks 2019]). Continue until descent or 24 hours after resolution of symptoms. Note: Some experts suggest 125 mg twice daily may be sufficient (Gallagher 2021).
High-altitude cerebral edema (adjunct):
Oral: 250 mg twice daily in combination with dexamethasone (WMS [Luks 2019]). Continue until descent or 24 hours after resolution of symptoms (Gallagher 2021).
Note: Although ER dosage formulations are FDA-approved for acute mountain sickness, the lowest available capsule dose (500 mg) exceeds current dosing recommendations for acute mountain sickness/high-altitude cerebral edema (WMS [Luks 2019]).
Elevated intraocular pressure associated with acute angle-closure glaucoma (adjunct):
Note: To be used when there is a ≥1-hour delay to ophthalmologist evaluation, as an adjunct to topical therapy (Weizer 2021).
Oral, IV: 500 mg once (Pokhrel 2007; Weizer 2021).
Idiopathic intracranial hypertension (off-label use):
Oral (immediate release, extended release): Initial: 250 to 500 mg twice daily; increase as tolerated by 250 mg every week to reach desired clinical effect or a maximum of 4 g/day (ten Hove 2016; Wall 2014).
Metabolic alkalosis (off-label use):
Note: In general, use after treatment of underlying causes and replacement of isotonic saline or potassium chloride when appropriate, or when additional fluids are contraindicated (Marik 1991; Mehta 2021).
IV (preferred), oral (immediate release): 500 mg as a single dose; may repeat as needed based upon acid-base status with 250 to 500 mg up to once or twice daily (Faisy 2016; Mazur 1999; Mehta 2021; Rialp Cervera 2017).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Note: Kidney function-adjusted dose recommendations are based on usual doses up to 1 g/day. There are no dosage adjustments necessary for any degree of kidney dysfunction for single doses of 500 mg (ie, elevated intraocular pressure or initial treatment of metabolic alkalosis) (expert opinion). Although the manufacturer’s labeling contraindicates use in severe kidney impairment, use may be considered in select patients after careful assessment of risks versus benefits along with close monitoring for adverse effects.
Altered kidney function (Chapron 1989; Yano 1998; expert opinion): Oral, IV:
CrCl ≥50 mL/minute: No dosage adjustment necessary.
CrCl 30 to <50 mL/minute:
Immediate release: 125 to 250 mg twice daily.
Extended release: Avoid use.
CrCl 10 to <30 mL/minute:
Immediate release: Avoid use; acetazolamide accumulation may result in CNS toxicity; if no alternatives available, may consider 125 mg twice daily with close monitoring.
Extended release: Avoid use.
CrCl <10 mL/minute:
Immediate release: Avoid use; acetazolamide accumulation may result in CNS toxicity; if no alternatives available, may consider 125 mg once daily with close monitoring.
Extended release: Avoid use.
Hemodialysis, intermittent (thrice weekly): Dialyzable (~30%) (Schwenk 1995; Vaziri 1980): Oral, IV:
Immediate release: Avoid use; acetazolamide accumulation may result in CNS toxicity; if no alternatives available, may consider 125 mg once daily with close monitoring; when scheduled dose falls on a dialysis day, administer after dialysis (Roy 1992; Schwenk 1995).
Extended release: Avoid use (expert opinion).
Peritoneal dialysis:
Oral, IV: Not significantly dialyzed (6.8%) (Schwenk 1994):
Immediate release: Avoid use; acetazolamide accumulation may result in CNS toxicity; if no alternatives available may consider 125 mg once daily with close monitoring (Schwenk 1994).
Extended release: Avoid use (expert opinion).
CRRT:
Oral, IV: Single doses of 500 mg for elevated intraocular pressure may be considered, otherwise, avoid use (expert opinion).
PIRRT (eg, sustained, low-efficiency diafiltration):
Oral, IV: Single doses of 500 mg for elevated intraocular pressure may be considered, otherwise, avoid use (expert opinion).
Use is contraindicated in patients with cirrhosis or marked liver disease or dysfunction.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule Extended Release 12 Hour, Oral:
Generic: 500 mg
Solution Reconstituted, Injection:
Generic: 500 mg (1 ea)
Solution Reconstituted, Injection [preservative free]:
Generic: 500 mg (1 ea)
Tablet, Oral:
Generic: 125 mg, 250 mg
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Injection:
Generic: 500 mg (1 ea)
Tablet, Oral:
Generic: 250 mg
Oral: Administer with food to decrease GI upset. Immediate-release tablets may be crushed and suspended in cherry or chocolate syrup to disguise the bitter taste of the drug; alternatively, submerge tablet in 10 mL of hot water and add 10 mL honey or syrup.
Parenteral:
IV: Direct IV injection is the preferred parenteral route of administration. Specific IV push rates are not provided in the manufacturer's labeling. In an adult trial, IV push rate of 500 mg over 3 minutes was used (Mazur 1999); some have recommended a maximum rate of 500 mg/minute (Gahart 2014). Additionally, a study in adults to assess cerebrovascular reserve used a rapid IV push of up to 1 g over ≤1 minute (Piepgras 1990).
IM: Not recommended as the drug's alkaline pH makes it very painful
Oral: May be administered with food. May cause an alteration in taste, especially carbonated beverages. Short-acting tablets may be crushed and suspended in cherry or chocolate syrup to disguise the bitter taste of the drug; do not use fruit juices. Alternatively, submerge tablet in 10 mL of hot water and add 10 mL honey or syrup.
IM: IM administration is painful because of the alkaline pH of the drug; use by this route is not recommended.
IV: Direct IV injection is the preferred parenteral route of administration. Specific IV push rates are not provided in the manufacturer's labeling. However, an IV push rate of up to 500 mg over 3 minutes has been reported in a clinical trial (Mazur 1999). Additionally, a study to assess cerebrovascular reserve used a rapid IV push of up to 1 g over ≤1 minute (Piepgras 1990).
Capsules, tablets: Store at controlled room temperature.
Injection: Store intact vials at 20°C to 25°C (68°F to 77°F). Store reconstituted solutions for 3 days under refrigeration at 2°C to 8°C (36°F to 46°F), or 12 hours at room temperature, 20°C to 25°C (68°F to 77°F).
Oral:
Immediate release tablets: Adjunct treatment of edema due to congestive heart failure, drug-induced edema, centrencephalic epilepsies, chronic simple (open-angle) glaucoma, secondary glaucoma, and preoperatively in acute angle-closure glaucoma where delay of surgery is desired (FDA approved in adults); prevention or amelioration of symptoms associated with acute mountain sickness (FDA approved in adults); treatment of metabolic alkalosis
Extended release capsules (Diamox Sequels): Adjunctive treatment of chronic simple (open-angle) glaucoma, secondary glaucoma, and preoperatively in acute angle-closure glaucoma where delay of surgery is desired (FDA approved in ages ≥12 years and adults); prevention or amelioration of symptoms associated with acute mountain sickness (FDA approved in ages ≥12 years and adults)
Parenteral: Adjunct treatment of edema due to congestive heart failure, drug-induced edema, centrencephalic epilepsies, chronic simple (open-angle) glaucoma, secondary glaucoma, and preoperatively in acute angle-closure glaucoma where delay of surgery is desired (FDA approved in adults); treatment of metabolic alkalosis
Acetazolamide may be confused with acetaminophen
Diamox [Canada and multiple international markets] may be confused with Diabinese brand name for chlorpropamide [Multiple international markets]; Dobutrex brand name for dobutamine [Multiple international markets]; Trimox brand name for amoxicillin [Brazil]; Zimox brand name for amoxicillin [Italy] and carbidopa/levodopa [Greece]
Case reports of aplastic anemia, including fatalities, have been reported with acetazolamide (Ref).
Mechanism: Non–dose-related; idiosyncratic. May be related to acetazolamide sulfonamide group (Ref).
Onset: Varied; has occurred within 7 weeks to a median of 3 months after treatment initiation (Ref).
Growth retardation (reduced height and/or weight) has been reported in children receiving chronic (>1 year) acetazolamide therapy for adjunctive treatment of seizures in combination with antiepileptic drug monotherapy. Growth returned to original level after discontinuation of acetazolamide (Ref).
Mechanism: Related to the pharmacologic action; may result in metabolic acidosis, possibly leading to growth retardation (Ref).
Immediate hypersensitivity reactions, including anaphylaxis and urticaria, have been reported with acetazolamide (Ref). Delayed hypersensitivity reactions range from maculopapular skin rash to rare severe cutaneous adverse reactions, including Stevens-Johnson syndrome, drug reaction with eosinophilia and systemic symptoms, and acute generalized exanthematous pustulosis (Ref).
Mechanism: Immediate hypersensitivity reactions: Non–dose-related; immunologic (ie, IgE-mediated, with specific antibodies formed against a drug allergen following initial exposure) (Ref). Delayed hypersensitivity reactions: Non–dose-related; immunologic (ie, involving a T-cell mediated drug-specific immune response) (Ref).
Onset: Immediate hypersensitivity reactions: Rapid; generally occurs within 1 hour of administration (Ref) but may occur up to 6 hours after exposure (Ref). Delayed hypersensitivity reactions: Varied; typically occur days to 8 weeks after drug exposure (Ref), but may occur more rapidly (usually within 1 to 4 days) upon reexposure (Ref).
Risk factors:
• Cross-reactivity: Limited published information regarding possible cross-reactivity between acetazolamide and other sulfonamides (Ref). Cross-reactivity between acetazolamide, a nonantibiotic sulfonamide, and antibiotic sulfonamides is unlikely to occur (Ref). Cross-reactivity among carbonic anhydrase inhibitors is unknown.
• Ethnicity: Increased risk in patients of Korean, Chinese, and Japanese descent (Ref).
Acetazolamide use has been associated with metabolic acidosis, which may lead to treatment discontinuation and, in some cases, death (Ref).
Mechanism: Related to pharmacologic action. Prevents bicarbonate reabsorption in the renal tubules, leading to metabolic acidosis (Ref).
Onset: Rapid; typically occurs within 2 to 4 days of therapy initiation (Ref).
Risk factors:
• Diabetes (Ref)
• Kidney impairment (Ref)
• Older adults (Ref)
• Uncompensated or severe COPD (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Frequency not defined:
Cardiovascular: Flushing
Dermatologic: Allergic skin reaction, skin photosensitivity
Endocrine & metabolic: Electrolyte disorder, glycosuria, hyperglycemia, hypoglycemia, hypokalemia, hyponatremia
Gastrointestinal: Decreased appetite, diarrhea, dysgeusia, melena, nausea, vomiting
Genitourinary: Crystalluria, hematuria
Hematologic & oncologic: Immune thrombocytopenia, leukopenia
Hepatic: Abnormal hepatic function tests, cholestatic jaundice, fulminant hepatic necrosis, hepatic insufficiency
Local: Pain at injection site
Nervous system: Ataxia, confusion, depression, dizziness, drowsiness, excitement, fatigue, flaccid paralysis, headache, malaise
Otic: Auditory disturbance, tinnitus
Renal: Polyuria
Miscellaneous: Fever
Postmarketing:
Dermatologic: Acute generalized exanthematous pustulosis (Jachiet 2013), maculopapular rash (Jachiet 2013), Stevens-Johnson syndrome (Her 2011), toxic epidermal necrolysis (Kim 2019), urticaria (Carlisle 2018)
Endocrine & metabolic: Growth retardation (children) (Futagi 1996), metabolic acidosis (Venkatesha 2000)
Hematologic & oncologic: Agranulocytosis (Incecik 2020), aplastic anemia (Keisu 1990), thrombocytopenia (Kodjikian 2004)
Hypersensitivity: Anaphylaxis (Gallerani 2002)
Immunologic: Drug reaction with eosinophilia and systemic symptoms (Ali 2021)
Nervous system: Paresthesia (Schmickl 2020)
Ophthalmic: Acute angle-closure glaucoma (Bayer 2010), choroidal effusion (Bayer 2010), myopia (Hill 2016)
Renal: Renal failure syndrome (Higenbottam 1978)
Hypersensitivity to acetazolamide, sulfonamides, or any component of the formulation; marked hepatic disease or insufficiency; decreased sodium and/or potassium levels; adrenocortical insufficiency; cirrhosis; hyperchloremic acidosis; severe renal disease or dysfunction; long-term use in noncongestive angle-closure glaucoma
Note: Although the FDA-approved product labeling states this medication is contraindicated in patients with hypersensitivity to sulfonamide-containing drugs, the scientific basis of this cross-sensitivity has been challenged. See “Warnings/Precautions” for more detail. Additionally, although the manufacturer’s labeling contraindicates use in severe kidney impairment, use may be considered in select patients after careful assessment of risks versus benefits along with close monitoring for adverse effects.
Canadian labeling: Additional contraindications not in US labeling: Hemorrhagic glaucoma; glaucoma due to peripheral anterior synechias; metabolic acidosis.
Concerns related to adverse effects:
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).
• Sulfonamide (“sulfa”) allergy: The FDA-approved product labeling for many medications containing a sulfonamide chemical group includes a broad contraindication in patients with a prior allergic reaction to sulfonamides. There is a potential for cross-reactivity between members of a specific class (eg, two antibiotic sulfonamides). However, concerns for cross-reactivity have previously extended to all compounds containing the sulfonamide structure (SO2NH2). An expanded understanding of allergic mechanisms indicates cross-reactivity between antibiotic sulfonamides and nonantibiotic sulfonamides may not occur or at the very least this potential is extremely low (Brackett 2004; Johnson 2005; Slatore 2004; Tornero 2004). In particular, mechanisms of cross-reaction due to antibody production (anaphylaxis) are unlikely to occur with nonantibiotic sulfonamides. T-cell-mediated (type IV) reactions (eg, maculopapular rash) are not well understood and it is not possible to completely exclude this potential based on current insights. In cases where prior reactions were severe (Stevens-Johnson syndrome/TEN), some clinicians choose to avoid exposure to these classes.
Disease-related concerns:
• Diabetes: Use with caution in patients with prediabetes or diabetes mellitus; may see a change in glucose control.
• Hepatic impairment: Use with caution in patients with hepatic dysfunction; in cirrhosis, avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy.
• Respiratory acidosis: Use with caution in patients with respiratory acidosis; may worsen acidosis.
Special populations:
• Elderly: Use with caution in the elderly; may be more sensitive to side effects.
Other warnings/precautions:
• Appropriate use: Increasing the dose does not increase diuresis and may increase the incidence of drowsiness and/or paresthesia; often results in a reduction of diuresis.
• IM administration: Painful because of the alkaline pH of the drug; use by this route is not recommended.
None known.
Ajmaline: Sulfonamides may enhance the adverse/toxic effect of Ajmaline. Specifically, the risk for cholestasis may be increased. Risk C: Monitor therapy
Alpha-/Beta-Agonists (Indirect-Acting): Carbonic Anhydrase Inhibitors may increase the serum concentration of Alpha-/Beta-Agonists (Indirect-Acting). Risk C: Monitor therapy
Amantadine: Carbonic Anhydrase Inhibitors may increase the serum concentration of Amantadine. Risk C: Monitor therapy
Amphetamines: Carbonic Anhydrase Inhibitors may decrease the excretion of Amphetamines. Risk C: Monitor therapy
CarBAMazepine: Carbonic Anhydrase Inhibitors may increase the serum concentration of CarBAMazepine. Risk C: Monitor therapy
Carbonic Anhydrase Inhibitors: May enhance the adverse/toxic effect of other Carbonic Anhydrase Inhibitors. The development of acid-base disorders with concurrent use of ophthalmic and oral carbonic anhydrase inhibitors has been reported. Management: Avoid concurrent use of different carbonic anhydrase inhibitors if possible. Monitor patients closely for the occurrence of kidney stones and with regards to severity of metabolic acidosis. Risk X: Avoid combination
CycloSPORINE (Systemic): AcetaZOLAMIDE may increase the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy
Desmopressin: Hyponatremia-Associated Agents may enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy
Dexketoprofen: May enhance the adverse/toxic effect of Sulfonamides. Risk C: Monitor therapy
Diacerein: May enhance the therapeutic effect of Diuretics. Specifically, the risk for dehydration or hypokalemia may be increased. Risk C: Monitor therapy
Flecainide: Carbonic Anhydrase Inhibitors may decrease the excretion of Flecainide. Risk C: Monitor therapy
Fosphenytoin-Phenytoin: Carbonic Anhydrase Inhibitors may enhance the adverse/toxic effect of Fosphenytoin-Phenytoin. Specifically, the risk for osteomalacia or rickets may be increased. Risk C: Monitor therapy
Lithium: Carbonic Anhydrase Inhibitors may decrease the serum concentration of Lithium. Risk C: Monitor therapy
Mecamylamine: Sulfonamides may enhance the adverse/toxic effect of Mecamylamine. Risk X: Avoid combination
Mefloquine: May diminish the therapeutic effect of Antiseizure Agents. Mefloquine may decrease the serum concentration of Antiseizure Agents. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of seizures. If antiseizure drugs are being used for another indication, monitor antiseizure drug concentrations and treatment response closely with concurrent use. Risk D: Consider therapy modification
Memantine: Carbonic Anhydrase Inhibitors may increase the serum concentration of Memantine. Risk C: Monitor therapy
MetFORMIN: Carbonic Anhydrase Inhibitors may enhance the adverse/toxic effect of MetFORMIN. Specifically, the risk of developing lactic acidosis may be increased. Risk C: Monitor therapy
Methenamine: Carbonic Anhydrase Inhibitors may diminish the therapeutic effect of Methenamine. Management: Consider avoiding this combination. Monitor for decreased therapeutic effects of methenamine if used concomitant with a carbonic anhydrase inhibitor. Risk D: Consider therapy modification
Mianserin: May diminish the therapeutic effect of Antiseizure Agents. Risk C: Monitor therapy
Opioid Agonists: May enhance the adverse/toxic effect of Diuretics. Opioid Agonists may diminish the therapeutic effect of Diuretics. Risk C: Monitor therapy
Orlistat: May decrease the serum concentration of Antiseizure Agents. Risk C: Monitor therapy
Primidone: Carbonic Anhydrase Inhibitors may enhance the adverse/toxic effect of Primidone. Specifically, osteomalacia and rickets. Carbonic Anhydrase Inhibitors may decrease the serum concentration of Primidone. Risk C: Monitor therapy
QuiNIDine: Carbonic Anhydrase Inhibitors may decrease the excretion of QuiNIDine. Risk C: Monitor therapy
Salicylates: May enhance the adverse/toxic effect of Carbonic Anhydrase Inhibitors. Salicylate toxicity might be enhanced by this same combination. Management: Avoid these combinations when possible.Dichlorphenamide use with high-dose aspirin as contraindicated. If another combination is used, monitor patients closely for adverse effects. Tachypnea, anorexia, lethargy, and coma have been reported. Risk D: Consider therapy modification
Sodium Bicarbonate: AcetaZOLAMIDE may enhance the adverse/toxic effect of Sodium Bicarbonate. Specifically, the risk of renal calculus formation may be increased. Risk C: Monitor therapy
Sodium Phosphates: Diuretics may enhance the nephrotoxic effect of Sodium Phosphates. Specifically, the risk of acute phosphate nephropathy may be enhanced. Management: Consider avoiding this combination by temporarily suspending treatment with diuretics, or seeking alternatives to oral sodium phosphate bowel preparation. If the combination cannot be avoided, hydrate adequately and monitor fluid and renal status. Risk D: Consider therapy modification
May be taken with food to decrease GI upset. May have additive effects with other folic acid antagonists. Some products may contain sodium.
Limited data is available following the use of acetazolamide in pregnant women for the treatment of idiopathic intracranial hypertension (Falardeau 2013; Kesler 2013).
Pregnant women exposed to acetazolamide during pregnancy for the treatment of seizure disorders are encouraged to enroll themselves into the AED Pregnancy Registry by calling 1-888-233-2334. Additional information is available at https://www.aedpregnancyregistry.org.
Serum electrolytes, CBC and platelet counts; intraocular pressure in glaucoma patients; monitor growth in pediatric patients
Reversible inhibition of the enzyme carbonic anhydrase resulting in reduction of hydrogen ion secretion at renal tubule and an increased renal excretion of sodium, potassium, bicarbonate, and water. Decreases production of aqueous humor and inhibits carbonic anhydrase in central nervous system to retard abnormal and excessive discharge from CNS neurons.
Onset of action: Capsule (extended release): 2 hours; Tablet (immediate release): 1 to 1.5 hours; IV: 2 to 10 minutes
Peak effect: Capsule (extended release): 8 to 18 hours; IV: 15 minutes; Tablet: 2 to 4 hours
Duration: Inhibition of aqueous humor secretion: Capsule (extended release): 18 to 24 hours; IV: 4 to 5 hours; Tablet: 8 to 12 hours
Absorption: Appears to be dose dependent; erratic with daily doses >10 mg/kg
Distribution: Erythrocytes, kidneys; blood-brain barrier
Protein binding: 95%
Half-life: 2.4 to 5.8 hours
Time to peak, plasma: Capsule (extended release): 3 to 6 hours; Tablet: 1 to 4 hours; IV: 15 minutes
Excretion: Urine (70% to 100% [IV, tablet], 47% [extended release capsule] as unchanged drug within 24 hours)
Sodium content of 500 mg injection: 2.049 mEq
A 25 mg/mL oral suspension may be made with tablets and either a 1:1 mixture of Ora-Sweet® and Ora-Plus® or a 1:1 mixture of Ora-Sweet® SF and Ora-Plus®. Crush twelve 250 mg tablets in a mortar and reduce to a fine powder. Add small portions of chosen vehicle and mix to a uniform paste; mix while adding the vehicle in incremental proportions to almost 120 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 120 mL. Label “shake well” and “refrigerate”. Stable for 60 days (Allen, 1996). When diluted in 120 mL solution of cherry syrup concentrate diluted 1:4 with simple syrup, NF, it is stable 60 days refrigerated (preferred) or at room temperature (Nahata, 2004).
Capsule, 12-hour (acetaZOLAMIDE ER Oral)
500 mg (per each): $0.82 - $4.29
Solution (reconstituted) (acetaZOLAMIDE Sodium Injection)
500 mg (per each): $39.38 - $52.75
Tablets (acetaZOLAMIDE Oral)
125 mg (per each): $2.09 - $2.18
250 mg (per each): $2.76 - $6.65
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.