MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
AcetaZOLAMIDE may be confused with acetoHEXAMIDE
Diamox® Sequels® may be confused with Diabinese®, Dobutrex®, Trimox®
U.S. BRAND NAMES — Diamox® Sequels®
PHARMACOLOGIC CATEGORY
Anticonvulsant, Miscellaneous
Carbonic Anhydrase Inhibitor
Diuretic, Carbonic Anhydrase Inhibitor
Ophthalmic Agent, Antiglaucoma
DOSING: ADULTS — Note: I.M. administration is not recommended.
Glaucoma:
Chronic simple (open-angle): Oral: 250 mg 1-4 times/day or 500 mg extended release capsule twice daily
Secondary, acute (closed-angle): I.V.: 250-500 mg, may repeat in 2-4 hours to a maximum of 1 g/day
Edema: Oral, I.V.: 250-375 mg once daily
Epilepsy: Oral: 8-30 mg/kg/day in 1-4 divided doses, not to exceed 1 g/day. Note: Extended release capsule is not recommended for treatment of epilepsy.
Metabolic alkalosis (unlabeled use): I.V. 250 mg every 6 hours for 4 doses or 500 mg single dose; reassess need based upon acid-base status
Mountain sickness: Oral: 250 mg every 8-12 hours (or 500 mg extended release capsules every 12-24 hours). Therapy should begin 24-48 hours before and continue during ascent and for at least 48 hours after arrival at the high altitude.
Note: In situations of rapid ascent (such as rescue or military operations), 1000 mg/day is recommended.
Urine alkalinization (unlabeled use): Oral: 5 mg/kg/dose repeated 2-3 times over 24 hours
Respiratory stimulant in COPD (unlabeled use): Oral, I.V.: 250 mg twice daily
DOSING: PEDIATRIC — Note: I.M. administration is not recommended.
(For additional information see "Acetazolamide: Pediatric drug information")
Glaucoma:
Oral: 8-30 mg/kg/day or 300-900 mg/m2/day divided every 8 hours
I.V.: 20-40 mg/kg/24 hours divided every 6 hours, not to exceed 1 g/day
Edema: Oral, I.V.: 5 mg/kg or 150 mg/m2 once every day
Epilepsy: Oral: Refer to adult dosing.
DOSING: ELDERLY — Oral: Initial: 250 mg once or twice daily; use lowest effective dose possible.
DOSING: RENAL IMPAIRMENT
Clcr 10-50 mL/minute: Administer every 12 hours.
Clcr <10 mL/minute: Avoid use (ineffective).
Moderately dialyzable (20% to 50%)
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, extended release: 500 mg
Diamox® Sequels®: 500 mg
Injection, powder for reconstitution: 500 mg
Tablet: 125 mg, 250 mg
DOSAGE FORMS: CONCISE
Capsule, extended release: 500 mg
Diamox® Sequels®: 500 mg
Injection, powder for reconstitution: 500 mg
Tablet: 125 mg, 250 mg
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION
Oral: 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.
I.M.: I.M. administration is painful because of the alkaline pH of the drug; use by this route is not recommended.
I.V.: No specific guidance given by manufacturer, but I.V. push at a rate of up to 500 mg over 3 minutes has been reported in a clinical trial (Mazur, 1999); a study to assess cerebrovascular reserve has used rapid I.V. push of up to 1 g over ≤ 1 minute (Piepgras, 1990)
COMPATIBILITY — Stable in dextran 6% in D5W, dextran 6% in NS, D5LR, D5NS, D51/2NS, D51/4NS, D5W, D10W, LR, NS, 1/2NS.
Y-site administration: Variable (consult detailed reference): Diltiazem, TPN.
Compatibility when admixed: Compatible: Cimetidine, ranitidine. Incompatible: Multivitamins.
USE — Treatment of glaucoma (chronic simple open-angle, secondary glaucoma, preoperatively in acute angle-closure); drug-induced edema or edema due to congestive heart failure (adjunctive therapy); centrencephalic epilepsies (immediate release dosage form); prevention or amelioration of symptoms associated with acute mountain sickness
USE - UNLABELED / INVESTIGATIONAL — Metabolic alkalosis; respiratory stimulant in COPD; urine alkalinization
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Cardiovascular: Flushing
Central nervous system: 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: Appetite decreased, diarrhea, melena, nausea, taste alteration, vomiting
Genitourinary: Crystalluria, glycosuria, hematuria, polyuria, renal failure
Hematologic: Agranulocytosis, aplastic anemia, leukopenia, thrombocytopenia, thrombocytopenic purpura
Hepatic: Cholestatic jaundice, fulminant hepatic necrosis, hepatic insufficiency, liver function tests abnormal
Local: Pain at injection site
Neuromuscular & skeletal: Flaccid paralysis, paresthesia
Ocular: Myopia
Otic: Hearing disturbance, tinnitus
Miscellaneous: Anaphylaxis
CONTRAINDICATIONS — Hypersensitivity to acetazolamide, sulfonamides, or any component of the formulation; hepatic disease or insufficiency; decreased sodium and/or potassium levels; adrenocortical insufficiency, cirrhosis; hyperchloremic acidosis, severe renal disease or dysfunction; severe pulmonary obstruction; long-term use in noncongestive angle-closure glaucoma
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: CNS effects: Impairment of mental alertness and/or physical coordination may occur. Sulfa allergy: Chemical similarities are present among sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop diuretics (except ethacrynic acid). Use in patients with sulfonylurea allergy is specifically contraindicated in product labeling, however, a risk of cross-reaction exists in patients with allergy to any of these compounds; avoid use when previous reaction has been severe. Discontinue if signs of hypersensitivity are noted.
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.
Special populations: Elderly: Use with caution in the elderly; may be more sensitive to side effects.
Other warnings/precautions: I.M. administration: Painful because of the alkaline pH of the drug; use by this route is not recommended.
METABOLISM / TRANSPORT EFFECTS — Inhibits CYP3A4 (weak)
DRUG INTERACTIONS
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Alpha-/Beta-Agonists: Carbonic Anhydrase Inhibitors may decrease the excretion of Alpha-/Beta-Agonists. Exceptions: Dipivefrin. Risk C: Monitor therapy
Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification
Amphetamines: Carbonic Anhydrase Inhibitors may decrease the excretion of Amphetamines. Risk C: Monitor therapy
Anticonvulsants (Barbiturate): Carbonic Anhydrase Inhibitors may enhance the adverse/toxic effect of Anticonvulsants (Barbiturate). Specifically, osteomalacia and rickets. Risk C: Monitor therapy
Anticonvulsants (Hydantoin): Carbonic Anhydrase Inhibitors may enhance the adverse/toxic effect of Anticonvulsants (Hydantoin). Specifically, osteomalacia and rickets. Risk C: Monitor therapy
Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy
CarBAMazepine: Carbonic Anhydrase Inhibitors may increase the serum concentration of CarBAMazepine. Risk C: Monitor therapy
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Flecainide: Carbonic Anhydrase Inhibitors may decrease the excretion of Flecainide. Risk C: Monitor therapy
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Ketorolac: May diminish the therapeutic effect of Anticonvulsants. Risk C: Monitor therapy
MAO Inhibitors: May enhance the orthostatic effect of Orthostasis Producing Agents. Risk C: Monitor therapy
Mefloquine: May diminish the therapeutic effect of Anticonvulsants. Mefloquine may decrease the serum concentration of Anticonvulsants. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of convulsions. Monitor anticonvulsant concentrations and treatment response closely with concurrent use. Risk D: Consider therapy modification
Memantine: Carbonic Anhydrase Inhibitors may decrease the excretion of Memantine. Risk C: Monitor therapy
Methenamine: Carbonic Anhydrase Inhibitors may diminish the therapeutic effect of Methenamine. Risk D: Consider therapy modification
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce dosage of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Risk D: Consider therapy modification
Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of Antihypertensives. 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
Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
QuiNIDine: Carbonic Anhydrase Inhibitors may decrease the excretion of QuiNIDine. Risk C: Monitor therapy
RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification
Salicylates: May enhance the adverse/toxic effect of Carbonic Anhydrase Inhibitors. Salicylate toxicity might be enhanced by this same combination. Risk D: Consider therapy modification
Trientine: Carbonic Anhydrase Inhibitor Diuretics may decrease the serum concentration of Trientine. Risk C: Monitor therapy
Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Teratogenic in animal studies, however, there are no adequate and well-controlled studies in pregnant women.
LACTATION — Enters breast milk/not recommended (AAP rates "compatible")
DIETARY CONSIDERATIONS — May be taken with food to decrease GI upset. May have additive effects with other folic acid antagonists. Sodium content of 500 mg injection: 47.2 mg (2.05 mEq).
PRICING — (data from drugstore.com)
Capsule, 12-hour (AcetaZOLAMIDE)
500 mg (100): $299.97
Capsule, 12-hour (Diamox Sequels)
500 mg (60): $314.98
Tablets (AcetaZOLAMIDE)
125 mg (90): $29.99
250 mg (60): $29.99
MONITORING PARAMETERS — Intraocular pressure, potassium, serum bicarbonate; serum electrolytes, periodic CBC with differential; monitor growth in pediatric patients
CANADIAN BRAND NAMES — Apo-Acetazolamide®; Diamox®
INTERNATIONAL BRAND NAMES — Acetadiazol (MX); Acetak (PE); Albox (JP); Apo-Acetazolamide (MY); Azol (TW); Carbinib (PT); Cetamid (PH); Diamox (AE, AR, AT, AU, BD, BE, BG, BH, BR, CH, CL, CO, CY, CZ, DE, DK, EG, ES, FI, FR, GB, GR, HK, HN, HR, ID, IE, IL, IN, IQ, IR, IT, JO, JP, KP, KW, LB, LU, LY, MY, NL, NO, OM, PH, PK, PT, QA, RU, SA, SE, SG, SY, TH, TR, TW, VE, YE, ZA); Diamox Sustets (CO); Diluran (CZ); Diural (UY); Diuramid (PL); Evamox (PK); Fonurit (HU); Glaupax (CH, DE, HR, JP, TH); Huma-Zolamide (HN, HU); Ledamox (JP); Lediamox (PT); Medene (TH); Optamide (PH); Renamid (HR); Stazol (PY); Synomax (IN); Uramox (IL); Zolmide (PH)
MECHANISM OF ACTION — 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 to decrease production of aqueous humor; also inhibits carbonic anhydrase in central nervous system to retard abnormal and excessive discharge from CNS neurons
PHARMACODYNAMICS / KINETICS
Onset of action: Capsule, extended release: 2 hours; I.V.: 2 minutes
Peak effect: Capsule, extended release: 8-12 hours; I.V.: 15 minutes; Tablet: 2-4 hours
Duration: Inhibition of aqueous humor secretion: Capsule, extended release: 18-24 hours; I.V.: 4-5 hours; Tablet: 8-12 hours
Distribution: Erythrocytes, kidneys; blood-brain barrier and placenta; distributes into milk (~30% of plasma concentrations)
Excretion: Urine (70% to 100% as unchanged drug)
PATIENT INFORMATION — Report numbness or tingling of extremities. Do not crush, chew, or swallow contents of long-acting capsule; may be opened and sprinkled on soft food. Ability to perform tasks requiring mental alertness and/or physical coordination may be impaired. Take with food; drug may cause substantial increase in blood glucose in some patients with diabetes.
Showing posts with label Acetazolamide. Show all posts
Showing posts with label Acetazolamide. Show all posts
Monday, May 17, 2010
Acetazolamide
MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
AcetaZOLAMIDE may be confused with acetoHEXAMIDE
Diamox® Sequels® may be confused with Diabinese®, Dobutrex®, Trimox®
U.S. BRAND NAMES — Diamox® Sequels®
PHARMACOLOGIC CATEGORY
Anticonvulsant, Miscellaneous
Carbonic Anhydrase Inhibitor
Diuretic, Carbonic Anhydrase Inhibitor
Ophthalmic Agent, Antiglaucoma
DOSING: ADULTS — Note: I.M. administration is not recommended.
Glaucoma:
Chronic simple (open-angle): Oral: 250 mg 1-4 times/day or 500 mg extended release capsule twice daily
Secondary, acute (closed-angle): I.V.: 250-500 mg, may repeat in 2-4 hours to a maximum of 1 g/day
Edema: Oral, I.V.: 250-375 mg once daily
Epilepsy: Oral: 8-30 mg/kg/day in 1-4 divided doses, not to exceed 1 g/day. Note: Extended release capsule is not recommended for treatment of epilepsy.
Metabolic alkalosis (unlabeled use): I.V. 250 mg every 6 hours for 4 doses or 500 mg single dose; reassess need based upon acid-base status
Mountain sickness: Oral: 250 mg every 8-12 hours (or 500 mg extended release capsules every 12-24 hours). Therapy should begin 24-48 hours before and continue during ascent and for at least 48 hours after arrival at the high altitude.
Note: In situations of rapid ascent (such as rescue or military operations), 1000 mg/day is recommended.
Urine alkalinization (unlabeled use): Oral: 5 mg/kg/dose repeated 2-3 times over 24 hours
Respiratory stimulant in COPD (unlabeled use): Oral, I.V.: 250 mg twice daily
DOSING: PEDIATRIC — Note: I.M. administration is not recommended.
(For additional information see "Acetazolamide: Pediatric drug information")
Glaucoma:
Oral: 8-30 mg/kg/day or 300-900 mg/m2/day divided every 8 hours
I.V.: 20-40 mg/kg/24 hours divided every 6 hours, not to exceed 1 g/day
Edema: Oral, I.V.: 5 mg/kg or 150 mg/m2 once every day
Epilepsy: Oral: Refer to adult dosing.
DOSING: ELDERLY — Oral: Initial: 250 mg once or twice daily; use lowest effective dose possible.
DOSING: RENAL IMPAIRMENT
Clcr 10-50 mL/minute: Administer every 12 hours.
Clcr <10 mL/minute: Avoid use (ineffective).
Moderately dialyzable (20% to 50%)
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, extended release: 500 mg
Diamox® Sequels®: 500 mg
Injection, powder for reconstitution: 500 mg
Tablet: 125 mg, 250 mg
DOSAGE FORMS: CONCISE
Capsule, extended release: 500 mg
Diamox® Sequels®: 500 mg
Injection, powder for reconstitution: 500 mg
Tablet: 125 mg, 250 mg
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION
Oral: 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.
I.M.: I.M. administration is painful because of the alkaline pH of the drug; use by this route is not recommended.
I.V.: No specific guidance given by manufacturer, but I.V. push at a rate of up to 500 mg over 3 minutes has been reported in a clinical trial (Mazur, 1999); a study to assess cerebrovascular reserve has used rapid I.V. push of up to 1 g over ≤ 1 minute (Piepgras, 1990)
COMPATIBILITY — Stable in dextran 6% in D5W, dextran 6% in NS, D5LR, D5NS, D51/2NS, D51/4NS, D5W, D10W, LR, NS, 1/2NS.
Y-site administration: Variable (consult detailed reference): Diltiazem, TPN.
Compatibility when admixed: Compatible: Cimetidine, ranitidine. Incompatible: Multivitamins.
USE — Treatment of glaucoma (chronic simple open-angle, secondary glaucoma, preoperatively in acute angle-closure); drug-induced edema or edema due to congestive heart failure (adjunctive therapy); centrencephalic epilepsies (immediate release dosage form); prevention or amelioration of symptoms associated with acute mountain sickness
USE - UNLABELED / INVESTIGATIONAL — Metabolic alkalosis; respiratory stimulant in COPD; urine alkalinization
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Cardiovascular: Flushing
Central nervous system: 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: Appetite decreased, diarrhea, melena, nausea, taste alteration, vomiting
Genitourinary: Crystalluria, glycosuria, hematuria, polyuria, renal failure
Hematologic: Agranulocytosis, aplastic anemia, leukopenia, thrombocytopenia, thrombocytopenic purpura
Hepatic: Cholestatic jaundice, fulminant hepatic necrosis, hepatic insufficiency, liver function tests abnormal
Local: Pain at injection site
Neuromuscular & skeletal: Flaccid paralysis, paresthesia
Ocular: Myopia
Otic: Hearing disturbance, tinnitus
Miscellaneous: Anaphylaxis
CONTRAINDICATIONS — Hypersensitivity to acetazolamide, sulfonamides, or any component of the formulation; hepatic disease or insufficiency; decreased sodium and/or potassium levels; adrenocortical insufficiency, cirrhosis; hyperchloremic acidosis, severe renal disease or dysfunction; severe pulmonary obstruction; long-term use in noncongestive angle-closure glaucoma
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: CNS effects: Impairment of mental alertness and/or physical coordination may occur. Sulfa allergy: Chemical similarities are present among sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop diuretics (except ethacrynic acid). Use in patients with sulfonylurea allergy is specifically contraindicated in product labeling, however, a risk of cross-reaction exists in patients with allergy to any of these compounds; avoid use when previous reaction has been severe. Discontinue if signs of hypersensitivity are noted.
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.
Special populations: Elderly: Use with caution in the elderly; may be more sensitive to side effects.
Other warnings/precautions: I.M. administration: Painful because of the alkaline pH of the drug; use by this route is not recommended.
METABOLISM / TRANSPORT EFFECTS — Inhibits CYP3A4 (weak)
DRUG INTERACTIONS
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Alpha-/Beta-Agonists: Carbonic Anhydrase Inhibitors may decrease the excretion of Alpha-/Beta-Agonists. Exceptions: Dipivefrin. Risk C: Monitor therapy
Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification
Amphetamines: Carbonic Anhydrase Inhibitors may decrease the excretion of Amphetamines. Risk C: Monitor therapy
Anticonvulsants (Barbiturate): Carbonic Anhydrase Inhibitors may enhance the adverse/toxic effect of Anticonvulsants (Barbiturate). Specifically, osteomalacia and rickets. Risk C: Monitor therapy
Anticonvulsants (Hydantoin): Carbonic Anhydrase Inhibitors may enhance the adverse/toxic effect of Anticonvulsants (Hydantoin). Specifically, osteomalacia and rickets. Risk C: Monitor therapy
Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy
CarBAMazepine: Carbonic Anhydrase Inhibitors may increase the serum concentration of CarBAMazepine. Risk C: Monitor therapy
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Flecainide: Carbonic Anhydrase Inhibitors may decrease the excretion of Flecainide. Risk C: Monitor therapy
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Ketorolac: May diminish the therapeutic effect of Anticonvulsants. Risk C: Monitor therapy
MAO Inhibitors: May enhance the orthostatic effect of Orthostasis Producing Agents. Risk C: Monitor therapy
Mefloquine: May diminish the therapeutic effect of Anticonvulsants. Mefloquine may decrease the serum concentration of Anticonvulsants. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of convulsions. Monitor anticonvulsant concentrations and treatment response closely with concurrent use. Risk D: Consider therapy modification
Memantine: Carbonic Anhydrase Inhibitors may decrease the excretion of Memantine. Risk C: Monitor therapy
Methenamine: Carbonic Anhydrase Inhibitors may diminish the therapeutic effect of Methenamine. Risk D: Consider therapy modification
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce dosage of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Risk D: Consider therapy modification
Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of Antihypertensives. 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
Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
QuiNIDine: Carbonic Anhydrase Inhibitors may decrease the excretion of QuiNIDine. Risk C: Monitor therapy
RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification
Salicylates: May enhance the adverse/toxic effect of Carbonic Anhydrase Inhibitors. Salicylate toxicity might be enhanced by this same combination. Risk D: Consider therapy modification
Trientine: Carbonic Anhydrase Inhibitor Diuretics may decrease the serum concentration of Trientine. Risk C: Monitor therapy
Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Teratogenic in animal studies, however, there are no adequate and well-controlled studies in pregnant women.
LACTATION — Enters breast milk/not recommended (AAP rates "compatible")
DIETARY CONSIDERATIONS — May be taken with food to decrease GI upset. May have additive effects with other folic acid antagonists. Sodium content of 500 mg injection: 47.2 mg (2.05 mEq).
PRICING — (data from drugstore.com)
Capsule, 12-hour (AcetaZOLAMIDE)
500 mg (100): $299.97
Capsule, 12-hour (Diamox Sequels)
500 mg (60): $314.98
Tablets (AcetaZOLAMIDE)
125 mg (90): $29.99
250 mg (60): $29.99
MONITORING PARAMETERS — Intraocular pressure, potassium, serum bicarbonate; serum electrolytes, periodic CBC with differential; monitor growth in pediatric patients
CANADIAN BRAND NAMES — Apo-Acetazolamide®; Diamox®
INTERNATIONAL BRAND NAMES — Acetadiazol (MX); Acetak (PE); Albox (JP); Apo-Acetazolamide (MY); Azol (TW); Carbinib (PT); Cetamid (PH); Diamox (AE, AR, AT, AU, BD, BE, BG, BH, BR, CH, CL, CO, CY, CZ, DE, DK, EG, ES, FI, FR, GB, GR, HK, HN, HR, ID, IE, IL, IN, IQ, IR, IT, JO, JP, KP, KW, LB, LU, LY, MY, NL, NO, OM, PH, PK, PT, QA, RU, SA, SE, SG, SY, TH, TR, TW, VE, YE, ZA); Diamox Sustets (CO); Diluran (CZ); Diural (UY); Diuramid (PL); Evamox (PK); Fonurit (HU); Glaupax (CH, DE, HR, JP, TH); Huma-Zolamide (HN, HU); Ledamox (JP); Lediamox (PT); Medene (TH); Optamide (PH); Renamid (HR); Stazol (PY); Synomax (IN); Uramox (IL); Zolmide (PH)
MECHANISM OF ACTION — 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 to decrease production of aqueous humor; also inhibits carbonic anhydrase in central nervous system to retard abnormal and excessive discharge from CNS neurons
PHARMACODYNAMICS / KINETICS
Onset of action: Capsule, extended release: 2 hours; I.V.: 2 minutes
Peak effect: Capsule, extended release: 8-12 hours; I.V.: 15 minutes; Tablet: 2-4 hours
Duration: Inhibition of aqueous humor secretion: Capsule, extended release: 18-24 hours; I.V.: 4-5 hours; Tablet: 8-12 hours
Distribution: Erythrocytes, kidneys; blood-brain barrier and placenta; distributes into milk (~30% of plasma concentrations)
Excretion: Urine (70% to 100% as unchanged drug)
PATIENT INFORMATION — Report numbness or tingling of extremities. Do not crush, chew, or swallow contents of long-acting capsule; may be opened and sprinkled on soft food. Ability to perform tasks requiring mental alertness and/or physical coordination may be impaired. Take with food; drug may cause substantial increase in blood glucose in some patients with diabetes.
Sound-alike/look-alike issues:
AcetaZOLAMIDE may be confused with acetoHEXAMIDE
Diamox® Sequels® may be confused with Diabinese®, Dobutrex®, Trimox®
U.S. BRAND NAMES — Diamox® Sequels®
PHARMACOLOGIC CATEGORY
Anticonvulsant, Miscellaneous
Carbonic Anhydrase Inhibitor
Diuretic, Carbonic Anhydrase Inhibitor
Ophthalmic Agent, Antiglaucoma
DOSING: ADULTS — Note: I.M. administration is not recommended.
Glaucoma:
Chronic simple (open-angle): Oral: 250 mg 1-4 times/day or 500 mg extended release capsule twice daily
Secondary, acute (closed-angle): I.V.: 250-500 mg, may repeat in 2-4 hours to a maximum of 1 g/day
Edema: Oral, I.V.: 250-375 mg once daily
Epilepsy: Oral: 8-30 mg/kg/day in 1-4 divided doses, not to exceed 1 g/day. Note: Extended release capsule is not recommended for treatment of epilepsy.
Metabolic alkalosis (unlabeled use): I.V. 250 mg every 6 hours for 4 doses or 500 mg single dose; reassess need based upon acid-base status
Mountain sickness: Oral: 250 mg every 8-12 hours (or 500 mg extended release capsules every 12-24 hours). Therapy should begin 24-48 hours before and continue during ascent and for at least 48 hours after arrival at the high altitude.
Note: In situations of rapid ascent (such as rescue or military operations), 1000 mg/day is recommended.
Urine alkalinization (unlabeled use): Oral: 5 mg/kg/dose repeated 2-3 times over 24 hours
Respiratory stimulant in COPD (unlabeled use): Oral, I.V.: 250 mg twice daily
DOSING: PEDIATRIC — Note: I.M. administration is not recommended.
(For additional information see "Acetazolamide: Pediatric drug information")
Glaucoma:
Oral: 8-30 mg/kg/day or 300-900 mg/m2/day divided every 8 hours
I.V.: 20-40 mg/kg/24 hours divided every 6 hours, not to exceed 1 g/day
Edema: Oral, I.V.: 5 mg/kg or 150 mg/m2 once every day
Epilepsy: Oral: Refer to adult dosing.
DOSING: ELDERLY — Oral: Initial: 250 mg once or twice daily; use lowest effective dose possible.
DOSING: RENAL IMPAIRMENT
Clcr 10-50 mL/minute: Administer every 12 hours.
Clcr <10 mL/minute: Avoid use (ineffective).
Moderately dialyzable (20% to 50%)
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, extended release: 500 mg
Diamox® Sequels®: 500 mg
Injection, powder for reconstitution: 500 mg
Tablet: 125 mg, 250 mg
DOSAGE FORMS: CONCISE
Capsule, extended release: 500 mg
Diamox® Sequels®: 500 mg
Injection, powder for reconstitution: 500 mg
Tablet: 125 mg, 250 mg
GENERIC EQUIVALENT AVAILABLE — Yes
ADMINISTRATION
Oral: 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.
I.M.: I.M. administration is painful because of the alkaline pH of the drug; use by this route is not recommended.
I.V.: No specific guidance given by manufacturer, but I.V. push at a rate of up to 500 mg over 3 minutes has been reported in a clinical trial (Mazur, 1999); a study to assess cerebrovascular reserve has used rapid I.V. push of up to 1 g over ≤ 1 minute (Piepgras, 1990)
COMPATIBILITY — Stable in dextran 6% in D5W, dextran 6% in NS, D5LR, D5NS, D51/2NS, D51/4NS, D5W, D10W, LR, NS, 1/2NS.
Y-site administration: Variable (consult detailed reference): Diltiazem, TPN.
Compatibility when admixed: Compatible: Cimetidine, ranitidine. Incompatible: Multivitamins.
USE — Treatment of glaucoma (chronic simple open-angle, secondary glaucoma, preoperatively in acute angle-closure); drug-induced edema or edema due to congestive heart failure (adjunctive therapy); centrencephalic epilepsies (immediate release dosage form); prevention or amelioration of symptoms associated with acute mountain sickness
USE - UNLABELED / INVESTIGATIONAL — Metabolic alkalosis; respiratory stimulant in COPD; urine alkalinization
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Cardiovascular: Flushing
Central nervous system: 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: Appetite decreased, diarrhea, melena, nausea, taste alteration, vomiting
Genitourinary: Crystalluria, glycosuria, hematuria, polyuria, renal failure
Hematologic: Agranulocytosis, aplastic anemia, leukopenia, thrombocytopenia, thrombocytopenic purpura
Hepatic: Cholestatic jaundice, fulminant hepatic necrosis, hepatic insufficiency, liver function tests abnormal
Local: Pain at injection site
Neuromuscular & skeletal: Flaccid paralysis, paresthesia
Ocular: Myopia
Otic: Hearing disturbance, tinnitus
Miscellaneous: Anaphylaxis
CONTRAINDICATIONS — Hypersensitivity to acetazolamide, sulfonamides, or any component of the formulation; hepatic disease or insufficiency; decreased sodium and/or potassium levels; adrenocortical insufficiency, cirrhosis; hyperchloremic acidosis, severe renal disease or dysfunction; severe pulmonary obstruction; long-term use in noncongestive angle-closure glaucoma
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: CNS effects: Impairment of mental alertness and/or physical coordination may occur. Sulfa allergy: Chemical similarities are present among sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop diuretics (except ethacrynic acid). Use in patients with sulfonylurea allergy is specifically contraindicated in product labeling, however, a risk of cross-reaction exists in patients with allergy to any of these compounds; avoid use when previous reaction has been severe. Discontinue if signs of hypersensitivity are noted.
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.
Special populations: Elderly: Use with caution in the elderly; may be more sensitive to side effects.
Other warnings/precautions: I.M. administration: Painful because of the alkaline pH of the drug; use by this route is not recommended.
METABOLISM / TRANSPORT EFFECTS — Inhibits CYP3A4 (weak)
DRUG INTERACTIONS
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Alpha-/Beta-Agonists: Carbonic Anhydrase Inhibitors may decrease the excretion of Alpha-/Beta-Agonists. Exceptions: Dipivefrin. Risk C: Monitor therapy
Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification
Amphetamines: Carbonic Anhydrase Inhibitors may decrease the excretion of Amphetamines. Risk C: Monitor therapy
Anticonvulsants (Barbiturate): Carbonic Anhydrase Inhibitors may enhance the adverse/toxic effect of Anticonvulsants (Barbiturate). Specifically, osteomalacia and rickets. Risk C: Monitor therapy
Anticonvulsants (Hydantoin): Carbonic Anhydrase Inhibitors may enhance the adverse/toxic effect of Anticonvulsants (Hydantoin). Specifically, osteomalacia and rickets. Risk C: Monitor therapy
Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy
CarBAMazepine: Carbonic Anhydrase Inhibitors may increase the serum concentration of CarBAMazepine. Risk C: Monitor therapy
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Flecainide: Carbonic Anhydrase Inhibitors may decrease the excretion of Flecainide. Risk C: Monitor therapy
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Ketorolac: May diminish the therapeutic effect of Anticonvulsants. Risk C: Monitor therapy
MAO Inhibitors: May enhance the orthostatic effect of Orthostasis Producing Agents. Risk C: Monitor therapy
Mefloquine: May diminish the therapeutic effect of Anticonvulsants. Mefloquine may decrease the serum concentration of Anticonvulsants. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of convulsions. Monitor anticonvulsant concentrations and treatment response closely with concurrent use. Risk D: Consider therapy modification
Memantine: Carbonic Anhydrase Inhibitors may decrease the excretion of Memantine. Risk C: Monitor therapy
Methenamine: Carbonic Anhydrase Inhibitors may diminish the therapeutic effect of Methenamine. Risk D: Consider therapy modification
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce dosage of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Risk D: Consider therapy modification
Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of Antihypertensives. 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
Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
QuiNIDine: Carbonic Anhydrase Inhibitors may decrease the excretion of QuiNIDine. Risk C: Monitor therapy
RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification
Salicylates: May enhance the adverse/toxic effect of Carbonic Anhydrase Inhibitors. Salicylate toxicity might be enhanced by this same combination. Risk D: Consider therapy modification
Trientine: Carbonic Anhydrase Inhibitor Diuretics may decrease the serum concentration of Trientine. Risk C: Monitor therapy
Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Teratogenic in animal studies, however, there are no adequate and well-controlled studies in pregnant women.
LACTATION — Enters breast milk/not recommended (AAP rates "compatible")
DIETARY CONSIDERATIONS — May be taken with food to decrease GI upset. May have additive effects with other folic acid antagonists. Sodium content of 500 mg injection: 47.2 mg (2.05 mEq).
PRICING — (data from drugstore.com)
Capsule, 12-hour (AcetaZOLAMIDE)
500 mg (100): $299.97
Capsule, 12-hour (Diamox Sequels)
500 mg (60): $314.98
Tablets (AcetaZOLAMIDE)
125 mg (90): $29.99
250 mg (60): $29.99
MONITORING PARAMETERS — Intraocular pressure, potassium, serum bicarbonate; serum electrolytes, periodic CBC with differential; monitor growth in pediatric patients
CANADIAN BRAND NAMES — Apo-Acetazolamide®; Diamox®
INTERNATIONAL BRAND NAMES — Acetadiazol (MX); Acetak (PE); Albox (JP); Apo-Acetazolamide (MY); Azol (TW); Carbinib (PT); Cetamid (PH); Diamox (AE, AR, AT, AU, BD, BE, BG, BH, BR, CH, CL, CO, CY, CZ, DE, DK, EG, ES, FI, FR, GB, GR, HK, HN, HR, ID, IE, IL, IN, IQ, IR, IT, JO, JP, KP, KW, LB, LU, LY, MY, NL, NO, OM, PH, PK, PT, QA, RU, SA, SE, SG, SY, TH, TR, TW, VE, YE, ZA); Diamox Sustets (CO); Diluran (CZ); Diural (UY); Diuramid (PL); Evamox (PK); Fonurit (HU); Glaupax (CH, DE, HR, JP, TH); Huma-Zolamide (HN, HU); Ledamox (JP); Lediamox (PT); Medene (TH); Optamide (PH); Renamid (HR); Stazol (PY); Synomax (IN); Uramox (IL); Zolmide (PH)
MECHANISM OF ACTION — 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 to decrease production of aqueous humor; also inhibits carbonic anhydrase in central nervous system to retard abnormal and excessive discharge from CNS neurons
PHARMACODYNAMICS / KINETICS
Onset of action: Capsule, extended release: 2 hours; I.V.: 2 minutes
Peak effect: Capsule, extended release: 8-12 hours; I.V.: 15 minutes; Tablet: 2-4 hours
Duration: Inhibition of aqueous humor secretion: Capsule, extended release: 18-24 hours; I.V.: 4-5 hours; Tablet: 8-12 hours
Distribution: Erythrocytes, kidneys; blood-brain barrier and placenta; distributes into milk (~30% of plasma concentrations)
Excretion: Urine (70% to 100% as unchanged drug)
PATIENT INFORMATION — Report numbness or tingling of extremities. Do not crush, chew, or swallow contents of long-acting capsule; may be opened and sprinkled on soft food. Ability to perform tasks requiring mental alertness and/or physical coordination may be impaired. Take with food; drug may cause substantial increase in blood glucose in some patients with diabetes.
Thursday, January 31, 2008
Acetazolamide
U.S. BRAND NAMES — Diamox® Sequels®
CANADIAN BRAND NAMES — Apo-Acetazolamide®; Diamox®
THERAPEUTIC CATEGORY Anticonvulsant, MiscellaneousCarbonic Anhydrase InhibitorDiuretic, Carbonic Anhydrase Inhibitor
DOSING
(For additional information see "Acetazolamide: Drug information")Children: Glaucoma: Oral: 8-30 mg/kg/day or 300-900 mg/m2/day divided every 8 hours I.V.: 20-40 mg/kg/day divided every 6 hours, not to exceed 1 g/day Edema: Oral, I.V.: 5 mg/kg/dose or 150 mg/m2/dose once daily Epilepsy: Oral: 4-16 mg/kg/day in 1-4 divided doses, not to exceed 30 mg/kg/day or 1 g/day; extended release capsule is not recommended for treatment of epilepsy
Adults: Glaucoma: Chronic simple (open-angle): Oral: 250 mg 1-4 times/day or 500 mg once followed by 125-250 mg every 4 hours, or 500 mg sustained release capsule twice daily Secondary, acute (closed-angle): I.V.: 250-500 mg, may repeat in 2-4 hours to a maximum of 1 g/day Edema: Oral, I.V.: 250-375 mg/day Epilepsy: Oral: 4-16 mg/kg/day in 1-4 divided doses, not to exceed 30 mg/kg/day or 1 g/day; extended release capsule is not recommended for treatment of epilepsy Altitude sickness: Oral: 500-1000 mg daily in divided doses such as 250 mg every 8-12 hours or 500 mg extended release capsules every 12-24 hours; therapy should begin 24-48 hours before and continued during ascent and for at least 48 hours after arrival at the high altitude Urine alkalinization: Oral: 5 mg/kg/dose repeated 2-3 times over 24 hours
Dosing interval in renal impairment: Children and Adults: Clcr 10-50 mL/minute: Administer every 12 hours Clcr <10 mL/minute: Avoid use
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, extended release: Diamox® Sequels®: 500 mg
Injection, powder for reconstitution: 500 mg
Tablet: 125 mg, 250 mg
GENERIC AVAILABLE — Yes: Injection, tablet
ADMINISTRATION Oral: Administer with food to decrease GI upset; tablet may be crushed and suspended in cherry or chocolate syrup to disguise the bitter taste of the drug (See Extemporaneous Preparations)
Parenteral: I.V.: Reconstitute with at least 5 mL SWI to provide a solution containing not more than 100 mg/mL; maximum concentration: 100 mg/mL; maximum rate of I.V. infusion: 500 mg/minute I.M.: Not generally recommended as the drug's alkaline pH makes it very painful
USE — Reduce elevated intraocular pressure in glaucoma; diuretic; adjunct to the treatment of refractory seizures; prevent acute altitude sickness; treatment of centrencephalic epilepsies; reduce CSF production in hydrocephalus
ADVERSE REACTIONS Cardiovascular: Cyanosis
Central nervous system: Drowsiness, ataxia, confusion, fatigue, vertigo, fever, seizures, dizziness, depression, malaise, headache, excitement
Dermatologic: Rash, erythema multiforme, photosensitivity, Stevens-Johnson syndrome (see Warnings), urticaria, toxic epidermal necrolysis
Endocrine & metabolic: Hypokalemia, hyperchloremic metabolic acidosis, hyperglycemia, hypoglycemia, growth retardation
Gastrointestinal: GI irritation, anorexia, nausea, vomiting, xerostomia, melena, dysgeusia, metallic taste, black stools
Genitourinary: Dysuria, polyuria
Hematologic: Bone marrow suppression, thrombocytopenia, hemolytic anemia, pancytopenia, agranulocytosis, leukopenia
Hepatic: Hepatic insufficiency, cholestatic jaundice, hepatic necrosis
Local: Pain at injection site
Neuromuscular & skeletal: Paresthesia, muscle weakness
Ocular: Myopia (transient)
Otic: Tinnitus
Renal: Renal calculi, phosphaturia, renal colic, hematuria, renal failure, polyuria
Respiratory: Hyperpnea
CONTRAINDICATIONS — Hypersensitivity to acetazolamide, any component, or other sulfonamides; patients with hepatic disease or insufficiency; decreased serum sodium and/or potassium; adrenocortical insufficiency; hyperchloremic acidosis; or severe renal disease; long-term administration in patients with chronic noncongestive angle-closure glaucoma
PRECAUTIONS — Use with caution in patients with respiratory acidosis, COPD, diabetes mellitus, and gout; reduce dosage in patients with renal impairment; growth retardation has been reported in children receiving chronic therapy (possibly due to chronic acidosis)
WARNINGS — Fatalities associated with sulfonamides, although rare, have occurred due to severe reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias; discontinue use at first sign of rash or any sign of adverse reaction. Anorexia, tachypnea, lethargy, metabolic acidosis, and death have been reported in patients receiving acetazolamide and high-dose aspirin concomittantly. Tolerance to antiepileptic effects may require dosage adjustment.
DRUG INTERACTIONS — Cytochrome P450 isoenzyme CYP3A4 inhibitor (weak)
Increases lithium excretion; may decrease the rate of excretion of other drugs such as procainamide, flecainide, quinidine, and tricyclic antidepressants; may increase the excretion of salicylates, amphetamine, and phenobarbital; may inactivate methenamine in the urine; may increase cyclosporine levels; may increase the risk of developing osteomalacia in patients receiving phenytoin or phenobarbital; topiramate may increase risk of nephrolithiasis and paresthesia; salicylates increase acetazolamide serum levels resulting in CNS toxicity; "high-dose" aspirin (see Warnings); ammonium chloride increases plasma concentration of nonionized acetazolamide; increased toxicity with propofol (cardiorespiratory instability); may increase effects of other folic acid antagonists
FOOD INTERACTIONS — Avoid natural licorice (causes sodium and water retention and increases potassium loss)
PREGNANCY RISK FACTOR — C (show table)
MONITORING PARAMETERS — Serum electrolytes, CBC and platelet counts
STABILITY — Store tablets and capsules at room temperature; after reconstitution, acetazolamide injection is stable for 12 hours at room temperature and for 1 week when refrigerated; physically incompatible with parenteral multivitamins
MECHANISM OF ACTION — Competitive, reversible inhibition of the enzyme carbonic anhydrase resulting in increased renal excretion of sodium, potassium, bicarbonate, and water and decreased formation of aqueous humor; also inhibits carbonic anhydrase in CNS to retard abnormal and excessive discharge from CNS neurons
PHARMACODYNAMICS Onset of action: Capsule, extended release: 2 hours Tablet: 1-1.5 hours I.V.: 2 minutes
Maximum effect: Capsule, extended release: 3-6 hours Tablet: 1-4 hours I.V.: 15 minutes
Duration: Capsule, extended release: 18-24 hours Tablet: 8-12 hours I.V.: 4-5 hours
PHARMACOKINETICS Absorption: Appears to be dose dependent; erratic with daily doses >10 mg/kg
Distribution: Into erythrocytes, kidneys, and breast milk (breast milk to plasma ratio of 0.25 has been reported); crosses the blood-brain barrier and the placenta
Protein binding: 95%
Half-life: 2.4-5.8 hours
Time to peak serum concentration: Tablet: 2-4 hours
Elimination: 70% to 100% of an I.V. or tablet dose and 47% of an extended release capsule excreted unchanged in urine within 24 hours
Dialysis: 20% to 50% removed by hemodialysis
TEST INTERACTIONS — May cause false-positive results for urinary protein with Albustix®, Labstix®, Albutest®, Bumintest®; interferes with HPLC method for assaying theophylline
PATIENT INFORMATION — Do not crush or chew long-acting capsule; may cause dry mouth. May rarely cause photosensitivity reactions (eg, exposure to sunlight may cause severe sunburn, skin rash, redness, or itching); avoid direct exposure to sunlight; may cause drowsiness and impair ability to perform activities requiring mental alertness or physical coordination
(For additional information see "Acetazolamide: Patient drug information")
ADDITIONAL INFORMATION — Sodium content of 500 mg injection: 2.049 mEq
Extended release capsules are indicated only for use for the adjunctive treatment of open-angle or secondary glaucoma and the prevention of high altitude sickness; avoid using extended release capsules for anticonvulsant or diuretic therapy
Acetazolamide has been used with questionable efficacy to slow the progression of hydrocephalus in neonates and infants who may not be good candidates for surgery. I.V. or oral doses of 5 mg/kg/dose every 6 hours increased by 25 mg/kg/day to a maximum of 100 mg/kg/day, if tolerated, have been used. Furosemide was used in combination with acetazolamide (Libenson, 1999).
EXTEMPORANEOUS PREPARATIONS A 25 mg/mL suspension may be made by crushing twelve 250 mg tablets and mixing with 120 mL of a 1:1 mixture of Ora-Sweet® and Ora-Plus® or a 1:1 mixture of Ora-Sweet® SF and Ora-Plus®. The resulting suspension is stable for 60 days refrigerated (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).
A 25 mg/mL suspension may be made by crushing one hundred 250 mg tablets; add 100 mL flavor/purified water; add a mixture of 10 g Veegum (already mixed with 200 mL purified water), 300 mL 1% methylcellulose and 300 mL syrup; qsad to 1000 mL with flavor/purified water and 10 mL paraben concentrate (methylparaben 120 mg, propylparaben 12 mg, propylene glycol qsad to 100 mL); stable 79 days refrigerated (Alexander, 1991). Allen LV and Erickson MA, "Stability of Acetazolamide, Allopurinol, Azathioprine, Clonazepam, and Flucytosine in Extemporaneously Compounded Oral Liquids,"Am J Health Sys Pharm, 1996, 53:1944-9. Alexander KS, Haribhakti RP, and Parker GA, "Stability of Acetazolamide in Suspension Compounded From Tablets,"Am J Hosp Pharm, 1991, 48(6):1241-4. Nahata, MC, Pai VB, and Hipple TF, Pediatric Drug Formulations, 5th ed, Cincinnati, OH: Harvey Whitney Books Co, 2004.
CANADIAN BRAND NAMES — Apo-Acetazolamide®; Diamox®
THERAPEUTIC CATEGORY Anticonvulsant, MiscellaneousCarbonic Anhydrase InhibitorDiuretic, Carbonic Anhydrase Inhibitor
DOSING
(For additional information see "Acetazolamide: Drug information")Children: Glaucoma: Oral: 8-30 mg/kg/day or 300-900 mg/m2/day divided every 8 hours I.V.: 20-40 mg/kg/day divided every 6 hours, not to exceed 1 g/day Edema: Oral, I.V.: 5 mg/kg/dose or 150 mg/m2/dose once daily Epilepsy: Oral: 4-16 mg/kg/day in 1-4 divided doses, not to exceed 30 mg/kg/day or 1 g/day; extended release capsule is not recommended for treatment of epilepsy
Adults: Glaucoma: Chronic simple (open-angle): Oral: 250 mg 1-4 times/day or 500 mg once followed by 125-250 mg every 4 hours, or 500 mg sustained release capsule twice daily Secondary, acute (closed-angle): I.V.: 250-500 mg, may repeat in 2-4 hours to a maximum of 1 g/day Edema: Oral, I.V.: 250-375 mg/day Epilepsy: Oral: 4-16 mg/kg/day in 1-4 divided doses, not to exceed 30 mg/kg/day or 1 g/day; extended release capsule is not recommended for treatment of epilepsy Altitude sickness: Oral: 500-1000 mg daily in divided doses such as 250 mg every 8-12 hours or 500 mg extended release capsules every 12-24 hours; therapy should begin 24-48 hours before and continued during ascent and for at least 48 hours after arrival at the high altitude Urine alkalinization: Oral: 5 mg/kg/dose repeated 2-3 times over 24 hours
Dosing interval in renal impairment: Children and Adults: Clcr 10-50 mL/minute: Administer every 12 hours Clcr <10 mL/minute: Avoid use
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, extended release: Diamox® Sequels®: 500 mg
Injection, powder for reconstitution: 500 mg
Tablet: 125 mg, 250 mg
GENERIC AVAILABLE — Yes: Injection, tablet
ADMINISTRATION Oral: Administer with food to decrease GI upset; tablet may be crushed and suspended in cherry or chocolate syrup to disguise the bitter taste of the drug (See Extemporaneous Preparations)
Parenteral: I.V.: Reconstitute with at least 5 mL SWI to provide a solution containing not more than 100 mg/mL; maximum concentration: 100 mg/mL; maximum rate of I.V. infusion: 500 mg/minute I.M.: Not generally recommended as the drug's alkaline pH makes it very painful
USE — Reduce elevated intraocular pressure in glaucoma; diuretic; adjunct to the treatment of refractory seizures; prevent acute altitude sickness; treatment of centrencephalic epilepsies; reduce CSF production in hydrocephalus
ADVERSE REACTIONS Cardiovascular: Cyanosis
Central nervous system: Drowsiness, ataxia, confusion, fatigue, vertigo, fever, seizures, dizziness, depression, malaise, headache, excitement
Dermatologic: Rash, erythema multiforme, photosensitivity, Stevens-Johnson syndrome (see Warnings), urticaria, toxic epidermal necrolysis
Endocrine & metabolic: Hypokalemia, hyperchloremic metabolic acidosis, hyperglycemia, hypoglycemia, growth retardation
Gastrointestinal: GI irritation, anorexia, nausea, vomiting, xerostomia, melena, dysgeusia, metallic taste, black stools
Genitourinary: Dysuria, polyuria
Hematologic: Bone marrow suppression, thrombocytopenia, hemolytic anemia, pancytopenia, agranulocytosis, leukopenia
Hepatic: Hepatic insufficiency, cholestatic jaundice, hepatic necrosis
Local: Pain at injection site
Neuromuscular & skeletal: Paresthesia, muscle weakness
Ocular: Myopia (transient)
Otic: Tinnitus
Renal: Renal calculi, phosphaturia, renal colic, hematuria, renal failure, polyuria
Respiratory: Hyperpnea
CONTRAINDICATIONS — Hypersensitivity to acetazolamide, any component, or other sulfonamides; patients with hepatic disease or insufficiency; decreased serum sodium and/or potassium; adrenocortical insufficiency; hyperchloremic acidosis; or severe renal disease; long-term administration in patients with chronic noncongestive angle-closure glaucoma
PRECAUTIONS — Use with caution in patients with respiratory acidosis, COPD, diabetes mellitus, and gout; reduce dosage in patients with renal impairment; growth retardation has been reported in children receiving chronic therapy (possibly due to chronic acidosis)
WARNINGS — Fatalities associated with sulfonamides, although rare, have occurred due to severe reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias; discontinue use at first sign of rash or any sign of adverse reaction. Anorexia, tachypnea, lethargy, metabolic acidosis, and death have been reported in patients receiving acetazolamide and high-dose aspirin concomittantly. Tolerance to antiepileptic effects may require dosage adjustment.
DRUG INTERACTIONS — Cytochrome P450 isoenzyme CYP3A4 inhibitor (weak)
Increases lithium excretion; may decrease the rate of excretion of other drugs such as procainamide, flecainide, quinidine, and tricyclic antidepressants; may increase the excretion of salicylates, amphetamine, and phenobarbital; may inactivate methenamine in the urine; may increase cyclosporine levels; may increase the risk of developing osteomalacia in patients receiving phenytoin or phenobarbital; topiramate may increase risk of nephrolithiasis and paresthesia; salicylates increase acetazolamide serum levels resulting in CNS toxicity; "high-dose" aspirin (see Warnings); ammonium chloride increases plasma concentration of nonionized acetazolamide; increased toxicity with propofol (cardiorespiratory instability); may increase effects of other folic acid antagonists
FOOD INTERACTIONS — Avoid natural licorice (causes sodium and water retention and increases potassium loss)
PREGNANCY RISK FACTOR — C (show table)
MONITORING PARAMETERS — Serum electrolytes, CBC and platelet counts
STABILITY — Store tablets and capsules at room temperature; after reconstitution, acetazolamide injection is stable for 12 hours at room temperature and for 1 week when refrigerated; physically incompatible with parenteral multivitamins
MECHANISM OF ACTION — Competitive, reversible inhibition of the enzyme carbonic anhydrase resulting in increased renal excretion of sodium, potassium, bicarbonate, and water and decreased formation of aqueous humor; also inhibits carbonic anhydrase in CNS to retard abnormal and excessive discharge from CNS neurons
PHARMACODYNAMICS Onset of action: Capsule, extended release: 2 hours Tablet: 1-1.5 hours I.V.: 2 minutes
Maximum effect: Capsule, extended release: 3-6 hours Tablet: 1-4 hours I.V.: 15 minutes
Duration: Capsule, extended release: 18-24 hours Tablet: 8-12 hours I.V.: 4-5 hours
PHARMACOKINETICS Absorption: Appears to be dose dependent; erratic with daily doses >10 mg/kg
Distribution: Into erythrocytes, kidneys, and breast milk (breast milk to plasma ratio of 0.25 has been reported); crosses the blood-brain barrier and the placenta
Protein binding: 95%
Half-life: 2.4-5.8 hours
Time to peak serum concentration: Tablet: 2-4 hours
Elimination: 70% to 100% of an I.V. or tablet dose and 47% of an extended release capsule excreted unchanged in urine within 24 hours
Dialysis: 20% to 50% removed by hemodialysis
TEST INTERACTIONS — May cause false-positive results for urinary protein with Albustix®, Labstix®, Albutest®, Bumintest®; interferes with HPLC method for assaying theophylline
PATIENT INFORMATION — Do not crush or chew long-acting capsule; may cause dry mouth. May rarely cause photosensitivity reactions (eg, exposure to sunlight may cause severe sunburn, skin rash, redness, or itching); avoid direct exposure to sunlight; may cause drowsiness and impair ability to perform activities requiring mental alertness or physical coordination
(For additional information see "Acetazolamide: Patient drug information")
ADDITIONAL INFORMATION — Sodium content of 500 mg injection: 2.049 mEq
Extended release capsules are indicated only for use for the adjunctive treatment of open-angle or secondary glaucoma and the prevention of high altitude sickness; avoid using extended release capsules for anticonvulsant or diuretic therapy
Acetazolamide has been used with questionable efficacy to slow the progression of hydrocephalus in neonates and infants who may not be good candidates for surgery. I.V. or oral doses of 5 mg/kg/dose every 6 hours increased by 25 mg/kg/day to a maximum of 100 mg/kg/day, if tolerated, have been used. Furosemide was used in combination with acetazolamide (Libenson, 1999).
EXTEMPORANEOUS PREPARATIONS A 25 mg/mL suspension may be made by crushing twelve 250 mg tablets and mixing with 120 mL of a 1:1 mixture of Ora-Sweet® and Ora-Plus® or a 1:1 mixture of Ora-Sweet® SF and Ora-Plus®. The resulting suspension is stable for 60 days refrigerated (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).
A 25 mg/mL suspension may be made by crushing one hundred 250 mg tablets; add 100 mL flavor/purified water; add a mixture of 10 g Veegum (already mixed with 200 mL purified water), 300 mL 1% methylcellulose and 300 mL syrup; qsad to 1000 mL with flavor/purified water and 10 mL paraben concentrate (methylparaben 120 mg, propylparaben 12 mg, propylene glycol qsad to 100 mL); stable 79 days refrigerated (Alexander, 1991). Allen LV and Erickson MA, "Stability of Acetazolamide, Allopurinol, Azathioprine, Clonazepam, and Flucytosine in Extemporaneously Compounded Oral Liquids,"Am J Health Sys Pharm, 1996, 53:1944-9. Alexander KS, Haribhakti RP, and Parker GA, "Stability of Acetazolamide in Suspension Compounded From Tablets,"Am J Hosp Pharm, 1991, 48(6):1241-4. Nahata, MC, Pai VB, and Hipple TF, Pediatric Drug Formulations, 5th ed, Cincinnati, OH: Harvey Whitney Books Co, 2004.
Acetazolamide
U.S. BRAND NAMES — Diamox® Sequels®
CANADIAN BRAND NAMES — Apo-Acetazolamide®; Diamox®
THERAPEUTIC CATEGORY Anticonvulsant, MiscellaneousCarbonic Anhydrase InhibitorDiuretic, Carbonic Anhydrase Inhibitor
DOSING
(For additional information see "Acetazolamide: Drug information")Children: Glaucoma: Oral: 8-30 mg/kg/day or 300-900 mg/m2/day divided every 8 hours I.V.: 20-40 mg/kg/day divided every 6 hours, not to exceed 1 g/day Edema: Oral, I.V.: 5 mg/kg/dose or 150 mg/m2/dose once daily Epilepsy: Oral: 4-16 mg/kg/day in 1-4 divided doses, not to exceed 30 mg/kg/day or 1 g/day; extended release capsule is not recommended for treatment of epilepsy
Adults: Glaucoma: Chronic simple (open-angle): Oral: 250 mg 1-4 times/day or 500 mg once followed by 125-250 mg every 4 hours, or 500 mg sustained release capsule twice daily Secondary, acute (closed-angle): I.V.: 250-500 mg, may repeat in 2-4 hours to a maximum of 1 g/day Edema: Oral, I.V.: 250-375 mg/day Epilepsy: Oral: 4-16 mg/kg/day in 1-4 divided doses, not to exceed 30 mg/kg/day or 1 g/day; extended release capsule is not recommended for treatment of epilepsy Altitude sickness: Oral: 500-1000 mg daily in divided doses such as 250 mg every 8-12 hours or 500 mg extended release capsules every 12-24 hours; therapy should begin 24-48 hours before and continued during ascent and for at least 48 hours after arrival at the high altitude Urine alkalinization: Oral: 5 mg/kg/dose repeated 2-3 times over 24 hours
Dosing interval in renal impairment: Children and Adults: Clcr 10-50 mL/minute: Administer every 12 hours Clcr <10 mL/minute: Avoid use
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, extended release: Diamox® Sequels®: 500 mg
Injection, powder for reconstitution: 500 mg
Tablet: 125 mg, 250 mg
GENERIC AVAILABLE — Yes: Injection, tablet
ADMINISTRATION Oral: Administer with food to decrease GI upset; tablet may be crushed and suspended in cherry or chocolate syrup to disguise the bitter taste of the drug (See Extemporaneous Preparations)
Parenteral: I.V.: Reconstitute with at least 5 mL SWI to provide a solution containing not more than 100 mg/mL; maximum concentration: 100 mg/mL; maximum rate of I.V. infusion: 500 mg/minute I.M.: Not generally recommended as the drug's alkaline pH makes it very painful
USE — Reduce elevated intraocular pressure in glaucoma; diuretic; adjunct to the treatment of refractory seizures; prevent acute altitude sickness; treatment of centrencephalic epilepsies; reduce CSF production in hydrocephalus
ADVERSE REACTIONS Cardiovascular: Cyanosis
Central nervous system: Drowsiness, ataxia, confusion, fatigue, vertigo, fever, seizures, dizziness, depression, malaise, headache, excitement
Dermatologic: Rash, erythema multiforme, photosensitivity, Stevens-Johnson syndrome (see Warnings), urticaria, toxic epidermal necrolysis
Endocrine & metabolic: Hypokalemia, hyperchloremic metabolic acidosis, hyperglycemia, hypoglycemia, growth retardation
Gastrointestinal: GI irritation, anorexia, nausea, vomiting, xerostomia, melena, dysgeusia, metallic taste, black stools
Genitourinary: Dysuria, polyuria
Hematologic: Bone marrow suppression, thrombocytopenia, hemolytic anemia, pancytopenia, agranulocytosis, leukopenia
Hepatic: Hepatic insufficiency, cholestatic jaundice, hepatic necrosis
Local: Pain at injection site
Neuromuscular & skeletal: Paresthesia, muscle weakness
Ocular: Myopia (transient)
Otic: Tinnitus
Renal: Renal calculi, phosphaturia, renal colic, hematuria, renal failure, polyuria
Respiratory: Hyperpnea
CONTRAINDICATIONS — Hypersensitivity to acetazolamide, any component, or other sulfonamides; patients with hepatic disease or insufficiency; decreased serum sodium and/or potassium; adrenocortical insufficiency; hyperchloremic acidosis; or severe renal disease; long-term administration in patients with chronic noncongestive angle-closure glaucoma
PRECAUTIONS — Use with caution in patients with respiratory acidosis, COPD, diabetes mellitus, and gout; reduce dosage in patients with renal impairment; growth retardation has been reported in children receiving chronic therapy (possibly due to chronic acidosis)
WARNINGS — Fatalities associated with sulfonamides, although rare, have occurred due to severe reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias; discontinue use at first sign of rash or any sign of adverse reaction. Anorexia, tachypnea, lethargy, metabolic acidosis, and death have been reported in patients receiving acetazolamide and high-dose aspirin concomittantly. Tolerance to antiepileptic effects may require dosage adjustment.
DRUG INTERACTIONS — Cytochrome P450 isoenzyme CYP3A4 inhibitor (weak)
Increases lithium excretion; may decrease the rate of excretion of other drugs such as procainamide, flecainide, quinidine, and tricyclic antidepressants; may increase the excretion of salicylates, amphetamine, and phenobarbital; may inactivate methenamine in the urine; may increase cyclosporine levels; may increase the risk of developing osteomalacia in patients receiving phenytoin or phenobarbital; topiramate may increase risk of nephrolithiasis and paresthesia; salicylates increase acetazolamide serum levels resulting in CNS toxicity; "high-dose" aspirin (see Warnings); ammonium chloride increases plasma concentration of nonionized acetazolamide; increased toxicity with propofol (cardiorespiratory instability); may increase effects of other folic acid antagonists
FOOD INTERACTIONS — Avoid natural licorice (causes sodium and water retention and increases potassium loss)
PREGNANCY RISK FACTOR — C (show table)
MONITORING PARAMETERS — Serum electrolytes, CBC and platelet counts
STABILITY — Store tablets and capsules at room temperature; after reconstitution, acetazolamide injection is stable for 12 hours at room temperature and for 1 week when refrigerated; physically incompatible with parenteral multivitamins
MECHANISM OF ACTION — Competitive, reversible inhibition of the enzyme carbonic anhydrase resulting in increased renal excretion of sodium, potassium, bicarbonate, and water and decreased formation of aqueous humor; also inhibits carbonic anhydrase in CNS to retard abnormal and excessive discharge from CNS neurons
PHARMACODYNAMICS Onset of action: Capsule, extended release: 2 hours Tablet: 1-1.5 hours I.V.: 2 minutes
Maximum effect: Capsule, extended release: 3-6 hours Tablet: 1-4 hours I.V.: 15 minutes
Duration: Capsule, extended release: 18-24 hours Tablet: 8-12 hours I.V.: 4-5 hours
PHARMACOKINETICS Absorption: Appears to be dose dependent; erratic with daily doses >10 mg/kg
Distribution: Into erythrocytes, kidneys, and breast milk (breast milk to plasma ratio of 0.25 has been reported); crosses the blood-brain barrier and the placenta
Protein binding: 95%
Half-life: 2.4-5.8 hours
Time to peak serum concentration: Tablet: 2-4 hours
Elimination: 70% to 100% of an I.V. or tablet dose and 47% of an extended release capsule excreted unchanged in urine within 24 hours
Dialysis: 20% to 50% removed by hemodialysis
TEST INTERACTIONS — May cause false-positive results for urinary protein with Albustix®, Labstix®, Albutest®, Bumintest®; interferes with HPLC method for assaying theophylline
PATIENT INFORMATION — Do not crush or chew long-acting capsule; may cause dry mouth. May rarely cause photosensitivity reactions (eg, exposure to sunlight may cause severe sunburn, skin rash, redness, or itching); avoid direct exposure to sunlight; may cause drowsiness and impair ability to perform activities requiring mental alertness or physical coordination
(For additional information see "Acetazolamide: Patient drug information")
ADDITIONAL INFORMATION — Sodium content of 500 mg injection: 2.049 mEq
Extended release capsules are indicated only for use for the adjunctive treatment of open-angle or secondary glaucoma and the prevention of high altitude sickness; avoid using extended release capsules for anticonvulsant or diuretic therapy
Acetazolamide has been used with questionable efficacy to slow the progression of hydrocephalus in neonates and infants who may not be good candidates for surgery. I.V. or oral doses of 5 mg/kg/dose every 6 hours increased by 25 mg/kg/day to a maximum of 100 mg/kg/day, if tolerated, have been used. Furosemide was used in combination with acetazolamide (Libenson, 1999).
EXTEMPORANEOUS PREPARATIONS A 25 mg/mL suspension may be made by crushing twelve 250 mg tablets and mixing with 120 mL of a 1:1 mixture of Ora-Sweet® and Ora-Plus® or a 1:1 mixture of Ora-Sweet® SF and Ora-Plus®. The resulting suspension is stable for 60 days refrigerated (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).
A 25 mg/mL suspension may be made by crushing one hundred 250 mg tablets; add 100 mL flavor/purified water; add a mixture of 10 g Veegum (already mixed with 200 mL purified water), 300 mL 1% methylcellulose and 300 mL syrup; qsad to 1000 mL with flavor/purified water and 10 mL paraben concentrate (methylparaben 120 mg, propylparaben 12 mg, propylene glycol qsad to 100 mL); stable 79 days refrigerated (Alexander, 1991). Allen LV and Erickson MA, "Stability of Acetazolamide, Allopurinol, Azathioprine, Clonazepam, and Flucytosine in Extemporaneously Compounded Oral Liquids,"Am J Health Sys Pharm, 1996, 53:1944-9. Alexander KS, Haribhakti RP, and Parker GA, "Stability of Acetazolamide in Suspension Compounded From Tablets,"Am J Hosp Pharm, 1991, 48(6):1241-4. Nahata, MC, Pai VB, and Hipple TF, Pediatric Drug Formulations, 5th ed, Cincinnati, OH: Harvey Whitney Books Co, 2004.
CANADIAN BRAND NAMES — Apo-Acetazolamide®; Diamox®
THERAPEUTIC CATEGORY Anticonvulsant, MiscellaneousCarbonic Anhydrase InhibitorDiuretic, Carbonic Anhydrase Inhibitor
DOSING
(For additional information see "Acetazolamide: Drug information")Children: Glaucoma: Oral: 8-30 mg/kg/day or 300-900 mg/m2/day divided every 8 hours I.V.: 20-40 mg/kg/day divided every 6 hours, not to exceed 1 g/day Edema: Oral, I.V.: 5 mg/kg/dose or 150 mg/m2/dose once daily Epilepsy: Oral: 4-16 mg/kg/day in 1-4 divided doses, not to exceed 30 mg/kg/day or 1 g/day; extended release capsule is not recommended for treatment of epilepsy
Adults: Glaucoma: Chronic simple (open-angle): Oral: 250 mg 1-4 times/day or 500 mg once followed by 125-250 mg every 4 hours, or 500 mg sustained release capsule twice daily Secondary, acute (closed-angle): I.V.: 250-500 mg, may repeat in 2-4 hours to a maximum of 1 g/day Edema: Oral, I.V.: 250-375 mg/day Epilepsy: Oral: 4-16 mg/kg/day in 1-4 divided doses, not to exceed 30 mg/kg/day or 1 g/day; extended release capsule is not recommended for treatment of epilepsy Altitude sickness: Oral: 500-1000 mg daily in divided doses such as 250 mg every 8-12 hours or 500 mg extended release capsules every 12-24 hours; therapy should begin 24-48 hours before and continued during ascent and for at least 48 hours after arrival at the high altitude Urine alkalinization: Oral: 5 mg/kg/dose repeated 2-3 times over 24 hours
Dosing interval in renal impairment: Children and Adults: Clcr 10-50 mL/minute: Administer every 12 hours Clcr <10 mL/minute: Avoid use
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, extended release: Diamox® Sequels®: 500 mg
Injection, powder for reconstitution: 500 mg
Tablet: 125 mg, 250 mg
GENERIC AVAILABLE — Yes: Injection, tablet
ADMINISTRATION Oral: Administer with food to decrease GI upset; tablet may be crushed and suspended in cherry or chocolate syrup to disguise the bitter taste of the drug (See Extemporaneous Preparations)
Parenteral: I.V.: Reconstitute with at least 5 mL SWI to provide a solution containing not more than 100 mg/mL; maximum concentration: 100 mg/mL; maximum rate of I.V. infusion: 500 mg/minute I.M.: Not generally recommended as the drug's alkaline pH makes it very painful
USE — Reduce elevated intraocular pressure in glaucoma; diuretic; adjunct to the treatment of refractory seizures; prevent acute altitude sickness; treatment of centrencephalic epilepsies; reduce CSF production in hydrocephalus
ADVERSE REACTIONS Cardiovascular: Cyanosis
Central nervous system: Drowsiness, ataxia, confusion, fatigue, vertigo, fever, seizures, dizziness, depression, malaise, headache, excitement
Dermatologic: Rash, erythema multiforme, photosensitivity, Stevens-Johnson syndrome (see Warnings), urticaria, toxic epidermal necrolysis
Endocrine & metabolic: Hypokalemia, hyperchloremic metabolic acidosis, hyperglycemia, hypoglycemia, growth retardation
Gastrointestinal: GI irritation, anorexia, nausea, vomiting, xerostomia, melena, dysgeusia, metallic taste, black stools
Genitourinary: Dysuria, polyuria
Hematologic: Bone marrow suppression, thrombocytopenia, hemolytic anemia, pancytopenia, agranulocytosis, leukopenia
Hepatic: Hepatic insufficiency, cholestatic jaundice, hepatic necrosis
Local: Pain at injection site
Neuromuscular & skeletal: Paresthesia, muscle weakness
Ocular: Myopia (transient)
Otic: Tinnitus
Renal: Renal calculi, phosphaturia, renal colic, hematuria, renal failure, polyuria
Respiratory: Hyperpnea
CONTRAINDICATIONS — Hypersensitivity to acetazolamide, any component, or other sulfonamides; patients with hepatic disease or insufficiency; decreased serum sodium and/or potassium; adrenocortical insufficiency; hyperchloremic acidosis; or severe renal disease; long-term administration in patients with chronic noncongestive angle-closure glaucoma
PRECAUTIONS — Use with caution in patients with respiratory acidosis, COPD, diabetes mellitus, and gout; reduce dosage in patients with renal impairment; growth retardation has been reported in children receiving chronic therapy (possibly due to chronic acidosis)
WARNINGS — Fatalities associated with sulfonamides, although rare, have occurred due to severe reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias; discontinue use at first sign of rash or any sign of adverse reaction. Anorexia, tachypnea, lethargy, metabolic acidosis, and death have been reported in patients receiving acetazolamide and high-dose aspirin concomittantly. Tolerance to antiepileptic effects may require dosage adjustment.
DRUG INTERACTIONS — Cytochrome P450 isoenzyme CYP3A4 inhibitor (weak)
Increases lithium excretion; may decrease the rate of excretion of other drugs such as procainamide, flecainide, quinidine, and tricyclic antidepressants; may increase the excretion of salicylates, amphetamine, and phenobarbital; may inactivate methenamine in the urine; may increase cyclosporine levels; may increase the risk of developing osteomalacia in patients receiving phenytoin or phenobarbital; topiramate may increase risk of nephrolithiasis and paresthesia; salicylates increase acetazolamide serum levels resulting in CNS toxicity; "high-dose" aspirin (see Warnings); ammonium chloride increases plasma concentration of nonionized acetazolamide; increased toxicity with propofol (cardiorespiratory instability); may increase effects of other folic acid antagonists
FOOD INTERACTIONS — Avoid natural licorice (causes sodium and water retention and increases potassium loss)
PREGNANCY RISK FACTOR — C (show table)
MONITORING PARAMETERS — Serum electrolytes, CBC and platelet counts
STABILITY — Store tablets and capsules at room temperature; after reconstitution, acetazolamide injection is stable for 12 hours at room temperature and for 1 week when refrigerated; physically incompatible with parenteral multivitamins
MECHANISM OF ACTION — Competitive, reversible inhibition of the enzyme carbonic anhydrase resulting in increased renal excretion of sodium, potassium, bicarbonate, and water and decreased formation of aqueous humor; also inhibits carbonic anhydrase in CNS to retard abnormal and excessive discharge from CNS neurons
PHARMACODYNAMICS Onset of action: Capsule, extended release: 2 hours Tablet: 1-1.5 hours I.V.: 2 minutes
Maximum effect: Capsule, extended release: 3-6 hours Tablet: 1-4 hours I.V.: 15 minutes
Duration: Capsule, extended release: 18-24 hours Tablet: 8-12 hours I.V.: 4-5 hours
PHARMACOKINETICS Absorption: Appears to be dose dependent; erratic with daily doses >10 mg/kg
Distribution: Into erythrocytes, kidneys, and breast milk (breast milk to plasma ratio of 0.25 has been reported); crosses the blood-brain barrier and the placenta
Protein binding: 95%
Half-life: 2.4-5.8 hours
Time to peak serum concentration: Tablet: 2-4 hours
Elimination: 70% to 100% of an I.V. or tablet dose and 47% of an extended release capsule excreted unchanged in urine within 24 hours
Dialysis: 20% to 50% removed by hemodialysis
TEST INTERACTIONS — May cause false-positive results for urinary protein with Albustix®, Labstix®, Albutest®, Bumintest®; interferes with HPLC method for assaying theophylline
PATIENT INFORMATION — Do not crush or chew long-acting capsule; may cause dry mouth. May rarely cause photosensitivity reactions (eg, exposure to sunlight may cause severe sunburn, skin rash, redness, or itching); avoid direct exposure to sunlight; may cause drowsiness and impair ability to perform activities requiring mental alertness or physical coordination
(For additional information see "Acetazolamide: Patient drug information")
ADDITIONAL INFORMATION — Sodium content of 500 mg injection: 2.049 mEq
Extended release capsules are indicated only for use for the adjunctive treatment of open-angle or secondary glaucoma and the prevention of high altitude sickness; avoid using extended release capsules for anticonvulsant or diuretic therapy
Acetazolamide has been used with questionable efficacy to slow the progression of hydrocephalus in neonates and infants who may not be good candidates for surgery. I.V. or oral doses of 5 mg/kg/dose every 6 hours increased by 25 mg/kg/day to a maximum of 100 mg/kg/day, if tolerated, have been used. Furosemide was used in combination with acetazolamide (Libenson, 1999).
EXTEMPORANEOUS PREPARATIONS A 25 mg/mL suspension may be made by crushing twelve 250 mg tablets and mixing with 120 mL of a 1:1 mixture of Ora-Sweet® and Ora-Plus® or a 1:1 mixture of Ora-Sweet® SF and Ora-Plus®. The resulting suspension is stable for 60 days refrigerated (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).
A 25 mg/mL suspension may be made by crushing one hundred 250 mg tablets; add 100 mL flavor/purified water; add a mixture of 10 g Veegum (already mixed with 200 mL purified water), 300 mL 1% methylcellulose and 300 mL syrup; qsad to 1000 mL with flavor/purified water and 10 mL paraben concentrate (methylparaben 120 mg, propylparaben 12 mg, propylene glycol qsad to 100 mL); stable 79 days refrigerated (Alexander, 1991). Allen LV and Erickson MA, "Stability of Acetazolamide, Allopurinol, Azathioprine, Clonazepam, and Flucytosine in Extemporaneously Compounded Oral Liquids,"Am J Health Sys Pharm, 1996, 53:1944-9. Alexander KS, Haribhakti RP, and Parker GA, "Stability of Acetazolamide in Suspension Compounded From Tablets,"Am J Hosp Pharm, 1991, 48(6):1241-4. Nahata, MC, Pai VB, and Hipple TF, Pediatric Drug Formulations, 5th ed, Cincinnati, OH: Harvey Whitney Books Co, 2004.
Sunday, January 20, 2008
Acetazolamide
U.S. BRAND NAMES — Diamox® Sequels®
PHARMACOLOGIC CATEGORY Anticonvulsant, MiscellaneousCarbonic Anhydrase InhibitorDiuretic, Carbonic Anhydrase InhibitorOphthalmic Agent, Antiglaucoma
DOSING: ADULTS — Note: I.M. administration is not recommended.
Glaucoma: Chronic simple (open-angle): Oral: 250 mg 1-4 times/day or 500 mg extended release capsule twice daily Secondary, acute (closed-angle): I.V.: 250-500 mg, may repeat in 2-4 hours to a maximum of 1 g/day
Edema: Oral, I.V.: 250-375 mg once daily
Epilepsy: Oral: 8-30 mg/kg/day in 1-4 divided doses, not to exceed 1 g/day. Note: Extended release capsule is not recommended for treatment of epilepsy.
Metabolic alkalosis (unlabeled use): I.V. 250 mg every 6 hours for 4 doses or 500 mg single dose; reassess need based upon acid-base status
Mountain sickness: Oral: 250 mg every 8-12 hours (or 500 mg extended release capsules every 12-24 hours). Therapy should begin 24-48 hours before and continue during ascent and for at least 48 hours after arrival at the high altitude. Note: In situations of rapid ascent (such as rescue or military operations), 1000 mg/day is recommended.
Urine alkalinization (unlabeled use): Oral: 5 mg/kg/dose repeated 2-3 times over 24 hours
Respiratory stimulant in COPD (unlabeled use): Oral, I.V.: 250 mg twice daily
DOSING: PEDIATRIC — Note: I.M. administration is not recommended.
(For additional information see "Acetazolamide: Pediatric drug information")
Glaucoma: Oral: 8-30 mg/kg/day or 300-900 mg/m2/day divided every 8 hours I.V.: 20-40 mg/kg/24 hours divided every 6 hours, not to exceed 1 g/day
Edema: Oral, I.V.: 5 mg/kg or 150 mg/m2 once every day
Epilepsy: Oral: Refer to adult dosing.
DOSING: ELDERLY — Oral: Initial: 250 mg once or twice daily; use lowest effective dose possible.
DOSING: RENAL IMPAIRMENT Clcr 10-50 mL/minute: Administer every 12 hours.
Clcr <10 mL/minute: Avoid use (ineffective).
Moderately dialyzable (20% to 50%)
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, extended release: Diamox® Sequels®: 500 mg
Injection, powder for reconstitution: 500 mg
Tablet: 125 mg, 250 mg
DOSAGE FORMS: CONCISE Capsule, extended release: Diamox® Sequels®: 500 mg
Injection, powder for reconstitution: 500 mg
Tablet: 125 mg, 250 mg
GENERIC EQUIVALENT AVAILABLE — Yes: Injection, tablet
ADMINISTRATION Oral: 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.
I.M.: I.M. administration is painful because of the alkaline pH of the drug; use by this route is not recommended.
COMPATIBILITY — Stable in dextran 6% in D5W, dextran 6% in NS, D5LR, D5NS, D51/2NS, D51/4NS, D5W, D10W, LR, NS, 1/2NS.
Y-site administration: Variable (consult detailed reference): Diltiazem, TPN.
Compatibility when admixed: Compatible: Cimetidine, ranitidine. Incompatible: Multivitamins.
USE — Treatment of glaucoma (chronic simple open-angle, secondary glaucoma, preoperatively in acute angle-closure); drug-induced edema or edema due to congestive heart failure (adjunctive therapy); centrencephalic epilepsies (immediate release dosage form); prevention or amelioration of symptoms associated with acute mountain sickness
USE - UNLABELED / INVESTIGATIONAL — Urine alkalinization; respiratory stimulant in COPD; metabolic alkalosis
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Cardiovascular: Flushing
Central nervous system: 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: Appetite decreased, diarrhea, melena, nausea, taste alteration, vomiting
Genitourinary: Crystalluria, glycosuria, hematuria, polyuria, renal failure
Hematologic: Agranulocytosis, aplastic anemia, leukopenia, thrombocytopenia, thrombocytopenic purpura
Hepatic: Cholestatic jaundice, fulminant hepatic necrosis, hepatic insufficiency, liver function tests abnormal
Local: Pain at injection site
Neuromuscular & skeletal: Flaccid paralysis, paresthesia
Ocular: Myopia
Otic: Hearing disturbance, tinnitus
Miscellaneous: Anaphylaxis
CONTRAINDICATIONS — Hypersensitivity to acetazolamide, sulfonamides, or any component of the formulation; hepatic disease or insufficiency; decreased sodium and/or potassium levels; adrenocortical insufficiency, cirrhosis; hyperchloremic acidosis, severe renal disease or dysfunction; severe pulmonary obstruction; long-term use in noncongestive angle-closure glaucoma
WARNINGS / PRECAUTIONS Concerns related to adverse effects: CNS effects: Impairment of mental alertness and/or physical coordination may occur. Sulfa allergy: Chemical similarities are present among sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop diuretics (except ethacrynic acid). Use in patients with sulfonylurea allergy is specifically contraindicated in product labeling, however, a risk of cross-reaction exists in patients with allergy to any of these compounds; avoid use when previous reaction has been severe. Discontinue if signs of hypersensitivity are noted.
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.
Special populations: Elderly: Use with caution in the elderly; may be more sensitive to side effects.
Other warnings/precautions: I.M. administration: Painful because of the alkaline pH of the drug; use by this route is not recommended.
DRUG INTERACTIONS — Inhibits CYP3A4 (weak)
Amphetamines: Urinary excretion of amphetamine may be decreased; magnitude and duration of effects may be enhanced.
Carbamazepine: May increase serum concentrations of carbamazepine.
Cyclosporine trough concentrations may be increased resulting in possible nephrotoxicity and neurotoxicity.
Flecainide: May decrease excretion of flecainide.
Lithium: Serum concentrations may be decreased by acetazolamide; monitor.
Memantine: May decrease excretion of memantine.
Methenamine: Urinary antiseptic effect may be prevented by acetazolamide.
Phenytoin: Serum concentrations of phenytoin may be increased; incidence of osteomalacia may be enhanced or increased in patients on chronic phenytoin therapy.
Primidone serum concentrations may be decreased; carbonic anhydrase inhibitors may enhance the adverse/toxic effects of primidone.
Quinidine: Urinary excretion of quinidine may be decreased and effects may be enhanced.
Salicylate use (high dose) may result in carbonic anhydrase inhibitor accumulation and toxicity including CNS depression and metabolic acidosis. Salicylate toxicity might also be enhanced.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Teratogenic in animal studies, however, there are no adequate and well-controlled studies in pregnant women.
LACTATION — Enters breast milk/not recommended (AAP rates "compatible")
DIETARY CONSIDERATIONS — May be taken with food to decrease GI upset. May have additive effects with other folic acid antagonists. Sodium content of 500 mg injection: 47.2 mg (2.05 mEq).
PRICING — (data from drugstore.com)Capsule, 12-hour (Diamox Sequels) 500 mg (60): $169.03
Tablets (AcetaZOLAMIDE) 125 mg (60): $8.98 250 mg (60): $18.99
MONITORING PARAMETERS — Intraocular pressure, potassium, serum bicarbonate; serum electrolytes, periodic CBC with differential; monitor growth in pediatric patients
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms include low blood sugar, tingling of lips and tongue, nausea, yawning, confusion, agitation, tachycardia, sweating, convulsions, stupor, and coma. Hypoglycemia should be managed with 50 mL I.V. dextrose 50% followed immediately with a continuous infusion of 10% dextrose in water (administer at a rate sufficient enough to approach a serum glucose level of 100 mg/dL). The use of corticosteroids to treat the hypoglycemia is controversial, however, the addition of 100 mg of hydrocortisone to the dextrose infusion may prove helpful. In certain instances, hemodialysis may be helpful.
CANADIAN BRAND NAMES — Apo-Acetazolamide®; Diamox®
INTERNATIONAL BRAND NAMES — Acetadiazol (MX); Albox (JP); Apo-Acetazolamide (CA, MY); Azol (TW); Carbinib (PT); Cetamid (PH); Defiltran (DE); Dehydratin (BG); Diamox (AE, AR, AT, AU, BE, BH, BR, CA, CH, CN, CO, CY, DK, EC, EG, ES, FI, FR, GB, HR, ID, IE, IN, IQ, IR, IT, JO, JP, KW, LB, LY, MX, MY, NL, NO, NZ, OM, PH, PY, QA, RU, SA, SE, SG, SY, TH, VE, YE, ZA); Diamox Sustets (CO); Diluran (CZ); Diural (UY); Diuramid (DE, PL); Edemox (ES); Evamox (PK); Genephamide (PE); Glaucomed (CO); Glaupax (CH, DK, HR, IE, JP, NO, TH); Huma-Zolamide (HU); Ledamox (JP); Lediamox (PT); Renamid (HR); Stazol (PY); Uramox (IL)
MECHANISM OF ACTION — 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 to decrease production of aqueous humor; also inhibits carbonic anhydrase in central nervous system to retard abnormal and excessive discharge from CNS neurons
PHARMACODYNAMICS / KINETICS Onset of action: Capsule, extended release: 2 hours; I.V.: 2 minutes Peak effect: Capsule, extended release: 8-12 hours; I.V.: 15 minutes; Tablet: 2-4 hours
Duration: Inhibition of aqueous humor secretion: Capsule, extended release: 18-24 hours; I.V.: 4-5 hours; Tablet: 8-12 hours
Distribution: Erythrocytes, kidneys; blood-brain barrier and placenta; distributes into milk (~30% of plasma concentrations)
Excretion: Urine (70% to 100% as unchanged drug)
PATIENT INFORMATION — Report numbness or tingling of extremities. Do not crush, chew, or swallow contents of long-acting capsule; may be opened and sprinkled on soft food. Ability to perform tasks requiring mental alertness and/or physical coordination may be impaired. Take with food; drug may cause substantial increase in blood glucose in some diabetic patients.
(For additional information see "Acetazolamide: Patient drug information")
PHARMACOLOGIC CATEGORY Anticonvulsant, MiscellaneousCarbonic Anhydrase InhibitorDiuretic, Carbonic Anhydrase InhibitorOphthalmic Agent, Antiglaucoma
DOSING: ADULTS — Note: I.M. administration is not recommended.
Glaucoma: Chronic simple (open-angle): Oral: 250 mg 1-4 times/day or 500 mg extended release capsule twice daily Secondary, acute (closed-angle): I.V.: 250-500 mg, may repeat in 2-4 hours to a maximum of 1 g/day
Edema: Oral, I.V.: 250-375 mg once daily
Epilepsy: Oral: 8-30 mg/kg/day in 1-4 divided doses, not to exceed 1 g/day. Note: Extended release capsule is not recommended for treatment of epilepsy.
Metabolic alkalosis (unlabeled use): I.V. 250 mg every 6 hours for 4 doses or 500 mg single dose; reassess need based upon acid-base status
Mountain sickness: Oral: 250 mg every 8-12 hours (or 500 mg extended release capsules every 12-24 hours). Therapy should begin 24-48 hours before and continue during ascent and for at least 48 hours after arrival at the high altitude. Note: In situations of rapid ascent (such as rescue or military operations), 1000 mg/day is recommended.
Urine alkalinization (unlabeled use): Oral: 5 mg/kg/dose repeated 2-3 times over 24 hours
Respiratory stimulant in COPD (unlabeled use): Oral, I.V.: 250 mg twice daily
DOSING: PEDIATRIC — Note: I.M. administration is not recommended.
(For additional information see "Acetazolamide: Pediatric drug information")
Glaucoma: Oral: 8-30 mg/kg/day or 300-900 mg/m2/day divided every 8 hours I.V.: 20-40 mg/kg/24 hours divided every 6 hours, not to exceed 1 g/day
Edema: Oral, I.V.: 5 mg/kg or 150 mg/m2 once every day
Epilepsy: Oral: Refer to adult dosing.
DOSING: ELDERLY — Oral: Initial: 250 mg once or twice daily; use lowest effective dose possible.
DOSING: RENAL IMPAIRMENT Clcr 10-50 mL/minute: Administer every 12 hours.
Clcr <10 mL/minute: Avoid use (ineffective).
Moderately dialyzable (20% to 50%)
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, extended release: Diamox® Sequels®: 500 mg
Injection, powder for reconstitution: 500 mg
Tablet: 125 mg, 250 mg
DOSAGE FORMS: CONCISE Capsule, extended release: Diamox® Sequels®: 500 mg
Injection, powder for reconstitution: 500 mg
Tablet: 125 mg, 250 mg
GENERIC EQUIVALENT AVAILABLE — Yes: Injection, tablet
ADMINISTRATION Oral: 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.
I.M.: I.M. administration is painful because of the alkaline pH of the drug; use by this route is not recommended.
COMPATIBILITY — Stable in dextran 6% in D5W, dextran 6% in NS, D5LR, D5NS, D51/2NS, D51/4NS, D5W, D10W, LR, NS, 1/2NS.
Y-site administration: Variable (consult detailed reference): Diltiazem, TPN.
Compatibility when admixed: Compatible: Cimetidine, ranitidine. Incompatible: Multivitamins.
USE — Treatment of glaucoma (chronic simple open-angle, secondary glaucoma, preoperatively in acute angle-closure); drug-induced edema or edema due to congestive heart failure (adjunctive therapy); centrencephalic epilepsies (immediate release dosage form); prevention or amelioration of symptoms associated with acute mountain sickness
USE - UNLABELED / INVESTIGATIONAL — Urine alkalinization; respiratory stimulant in COPD; metabolic alkalosis
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Cardiovascular: Flushing
Central nervous system: 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: Appetite decreased, diarrhea, melena, nausea, taste alteration, vomiting
Genitourinary: Crystalluria, glycosuria, hematuria, polyuria, renal failure
Hematologic: Agranulocytosis, aplastic anemia, leukopenia, thrombocytopenia, thrombocytopenic purpura
Hepatic: Cholestatic jaundice, fulminant hepatic necrosis, hepatic insufficiency, liver function tests abnormal
Local: Pain at injection site
Neuromuscular & skeletal: Flaccid paralysis, paresthesia
Ocular: Myopia
Otic: Hearing disturbance, tinnitus
Miscellaneous: Anaphylaxis
CONTRAINDICATIONS — Hypersensitivity to acetazolamide, sulfonamides, or any component of the formulation; hepatic disease or insufficiency; decreased sodium and/or potassium levels; adrenocortical insufficiency, cirrhosis; hyperchloremic acidosis, severe renal disease or dysfunction; severe pulmonary obstruction; long-term use in noncongestive angle-closure glaucoma
WARNINGS / PRECAUTIONS Concerns related to adverse effects: CNS effects: Impairment of mental alertness and/or physical coordination may occur. Sulfa allergy: Chemical similarities are present among sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop diuretics (except ethacrynic acid). Use in patients with sulfonylurea allergy is specifically contraindicated in product labeling, however, a risk of cross-reaction exists in patients with allergy to any of these compounds; avoid use when previous reaction has been severe. Discontinue if signs of hypersensitivity are noted.
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.
Special populations: Elderly: Use with caution in the elderly; may be more sensitive to side effects.
Other warnings/precautions: I.M. administration: Painful because of the alkaline pH of the drug; use by this route is not recommended.
DRUG INTERACTIONS — Inhibits CYP3A4 (weak)
Amphetamines: Urinary excretion of amphetamine may be decreased; magnitude and duration of effects may be enhanced.
Carbamazepine: May increase serum concentrations of carbamazepine.
Cyclosporine trough concentrations may be increased resulting in possible nephrotoxicity and neurotoxicity.
Flecainide: May decrease excretion of flecainide.
Lithium: Serum concentrations may be decreased by acetazolamide; monitor.
Memantine: May decrease excretion of memantine.
Methenamine: Urinary antiseptic effect may be prevented by acetazolamide.
Phenytoin: Serum concentrations of phenytoin may be increased; incidence of osteomalacia may be enhanced or increased in patients on chronic phenytoin therapy.
Primidone serum concentrations may be decreased; carbonic anhydrase inhibitors may enhance the adverse/toxic effects of primidone.
Quinidine: Urinary excretion of quinidine may be decreased and effects may be enhanced.
Salicylate use (high dose) may result in carbonic anhydrase inhibitor accumulation and toxicity including CNS depression and metabolic acidosis. Salicylate toxicity might also be enhanced.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Teratogenic in animal studies, however, there are no adequate and well-controlled studies in pregnant women.
LACTATION — Enters breast milk/not recommended (AAP rates "compatible")
DIETARY CONSIDERATIONS — May be taken with food to decrease GI upset. May have additive effects with other folic acid antagonists. Sodium content of 500 mg injection: 47.2 mg (2.05 mEq).
PRICING — (data from drugstore.com)Capsule, 12-hour (Diamox Sequels) 500 mg (60): $169.03
Tablets (AcetaZOLAMIDE) 125 mg (60): $8.98 250 mg (60): $18.99
MONITORING PARAMETERS — Intraocular pressure, potassium, serum bicarbonate; serum electrolytes, periodic CBC with differential; monitor growth in pediatric patients
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms include low blood sugar, tingling of lips and tongue, nausea, yawning, confusion, agitation, tachycardia, sweating, convulsions, stupor, and coma. Hypoglycemia should be managed with 50 mL I.V. dextrose 50% followed immediately with a continuous infusion of 10% dextrose in water (administer at a rate sufficient enough to approach a serum glucose level of 100 mg/dL). The use of corticosteroids to treat the hypoglycemia is controversial, however, the addition of 100 mg of hydrocortisone to the dextrose infusion may prove helpful. In certain instances, hemodialysis may be helpful.
CANADIAN BRAND NAMES — Apo-Acetazolamide®; Diamox®
INTERNATIONAL BRAND NAMES — Acetadiazol (MX); Albox (JP); Apo-Acetazolamide (CA, MY); Azol (TW); Carbinib (PT); Cetamid (PH); Defiltran (DE); Dehydratin (BG); Diamox (AE, AR, AT, AU, BE, BH, BR, CA, CH, CN, CO, CY, DK, EC, EG, ES, FI, FR, GB, HR, ID, IE, IN, IQ, IR, IT, JO, JP, KW, LB, LY, MX, MY, NL, NO, NZ, OM, PH, PY, QA, RU, SA, SE, SG, SY, TH, VE, YE, ZA); Diamox Sustets (CO); Diluran (CZ); Diural (UY); Diuramid (DE, PL); Edemox (ES); Evamox (PK); Genephamide (PE); Glaucomed (CO); Glaupax (CH, DK, HR, IE, JP, NO, TH); Huma-Zolamide (HU); Ledamox (JP); Lediamox (PT); Renamid (HR); Stazol (PY); Uramox (IL)
MECHANISM OF ACTION — 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 to decrease production of aqueous humor; also inhibits carbonic anhydrase in central nervous system to retard abnormal and excessive discharge from CNS neurons
PHARMACODYNAMICS / KINETICS Onset of action: Capsule, extended release: 2 hours; I.V.: 2 minutes Peak effect: Capsule, extended release: 8-12 hours; I.V.: 15 minutes; Tablet: 2-4 hours
Duration: Inhibition of aqueous humor secretion: Capsule, extended release: 18-24 hours; I.V.: 4-5 hours; Tablet: 8-12 hours
Distribution: Erythrocytes, kidneys; blood-brain barrier and placenta; distributes into milk (~30% of plasma concentrations)
Excretion: Urine (70% to 100% as unchanged drug)
PATIENT INFORMATION — Report numbness or tingling of extremities. Do not crush, chew, or swallow contents of long-acting capsule; may be opened and sprinkled on soft food. Ability to perform tasks requiring mental alertness and/or physical coordination may be impaired. Take with food; drug may cause substantial increase in blood glucose in some diabetic patients.
(For additional information see "Acetazolamide: Patient drug information")
Acetazolamide
U.S. BRAND NAMES — Diamox® Sequels®
PHARMACOLOGIC CATEGORY Anticonvulsant, MiscellaneousCarbonic Anhydrase InhibitorDiuretic, Carbonic Anhydrase InhibitorOphthalmic Agent, Antiglaucoma
DOSING: ADULTS — Note: I.M. administration is not recommended.
Glaucoma: Chronic simple (open-angle): Oral: 250 mg 1-4 times/day or 500 mg extended release capsule twice daily Secondary, acute (closed-angle): I.V.: 250-500 mg, may repeat in 2-4 hours to a maximum of 1 g/day
Edema: Oral, I.V.: 250-375 mg once daily
Epilepsy: Oral: 8-30 mg/kg/day in 1-4 divided doses, not to exceed 1 g/day. Note: Extended release capsule is not recommended for treatment of epilepsy.
Metabolic alkalosis (unlabeled use): I.V. 250 mg every 6 hours for 4 doses or 500 mg single dose; reassess need based upon acid-base status
Mountain sickness: Oral: 250 mg every 8-12 hours (or 500 mg extended release capsules every 12-24 hours). Therapy should begin 24-48 hours before and continue during ascent and for at least 48 hours after arrival at the high altitude. Note: In situations of rapid ascent (such as rescue or military operations), 1000 mg/day is recommended.
Urine alkalinization (unlabeled use): Oral: 5 mg/kg/dose repeated 2-3 times over 24 hours
Respiratory stimulant in COPD (unlabeled use): Oral, I.V.: 250 mg twice daily
DOSING: PEDIATRIC — Note: I.M. administration is not recommended.
(For additional information see "Acetazolamide: Pediatric drug information")
Glaucoma: Oral: 8-30 mg/kg/day or 300-900 mg/m2/day divided every 8 hours I.V.: 20-40 mg/kg/24 hours divided every 6 hours, not to exceed 1 g/day
Edema: Oral, I.V.: 5 mg/kg or 150 mg/m2 once every day
Epilepsy: Oral: Refer to adult dosing.
DOSING: ELDERLY — Oral: Initial: 250 mg once or twice daily; use lowest effective dose possible.
DOSING: RENAL IMPAIRMENT Clcr 10-50 mL/minute: Administer every 12 hours.
Clcr <10 mL/minute: Avoid use (ineffective).
Moderately dialyzable (20% to 50%)
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, extended release: Diamox® Sequels®: 500 mg
Injection, powder for reconstitution: 500 mg
Tablet: 125 mg, 250 mg
DOSAGE FORMS: CONCISE Capsule, extended release: Diamox® Sequels®: 500 mg
Injection, powder for reconstitution: 500 mg
Tablet: 125 mg, 250 mg
GENERIC EQUIVALENT AVAILABLE — Yes: Injection, tablet
ADMINISTRATION Oral: 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.
I.M.: I.M. administration is painful because of the alkaline pH of the drug; use by this route is not recommended.
COMPATIBILITY — Stable in dextran 6% in D5W, dextran 6% in NS, D5LR, D5NS, D51/2NS, D51/4NS, D5W, D10W, LR, NS, 1/2NS.
Y-site administration: Variable (consult detailed reference): Diltiazem, TPN.
Compatibility when admixed: Compatible: Cimetidine, ranitidine. Incompatible: Multivitamins.
USE — Treatment of glaucoma (chronic simple open-angle, secondary glaucoma, preoperatively in acute angle-closure); drug-induced edema or edema due to congestive heart failure (adjunctive therapy); centrencephalic epilepsies (immediate release dosage form); prevention or amelioration of symptoms associated with acute mountain sickness
USE - UNLABELED / INVESTIGATIONAL — Urine alkalinization; respiratory stimulant in COPD; metabolic alkalosis
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Cardiovascular: Flushing
Central nervous system: 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: Appetite decreased, diarrhea, melena, nausea, taste alteration, vomiting
Genitourinary: Crystalluria, glycosuria, hematuria, polyuria, renal failure
Hematologic: Agranulocytosis, aplastic anemia, leukopenia, thrombocytopenia, thrombocytopenic purpura
Hepatic: Cholestatic jaundice, fulminant hepatic necrosis, hepatic insufficiency, liver function tests abnormal
Local: Pain at injection site
Neuromuscular & skeletal: Flaccid paralysis, paresthesia
Ocular: Myopia
Otic: Hearing disturbance, tinnitus
Miscellaneous: Anaphylaxis
CONTRAINDICATIONS — Hypersensitivity to acetazolamide, sulfonamides, or any component of the formulation; hepatic disease or insufficiency; decreased sodium and/or potassium levels; adrenocortical insufficiency, cirrhosis; hyperchloremic acidosis, severe renal disease or dysfunction; severe pulmonary obstruction; long-term use in noncongestive angle-closure glaucoma
WARNINGS / PRECAUTIONS Concerns related to adverse effects: CNS effects: Impairment of mental alertness and/or physical coordination may occur. Sulfa allergy: Chemical similarities are present among sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop diuretics (except ethacrynic acid). Use in patients with sulfonylurea allergy is specifically contraindicated in product labeling, however, a risk of cross-reaction exists in patients with allergy to any of these compounds; avoid use when previous reaction has been severe. Discontinue if signs of hypersensitivity are noted.
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.
Special populations: Elderly: Use with caution in the elderly; may be more sensitive to side effects.
Other warnings/precautions: I.M. administration: Painful because of the alkaline pH of the drug; use by this route is not recommended.
DRUG INTERACTIONS — Inhibits CYP3A4 (weak)
Amphetamines: Urinary excretion of amphetamine may be decreased; magnitude and duration of effects may be enhanced.
Carbamazepine: May increase serum concentrations of carbamazepine.
Cyclosporine trough concentrations may be increased resulting in possible nephrotoxicity and neurotoxicity.
Flecainide: May decrease excretion of flecainide.
Lithium: Serum concentrations may be decreased by acetazolamide; monitor.
Memantine: May decrease excretion of memantine.
Methenamine: Urinary antiseptic effect may be prevented by acetazolamide.
Phenytoin: Serum concentrations of phenytoin may be increased; incidence of osteomalacia may be enhanced or increased in patients on chronic phenytoin therapy.
Primidone serum concentrations may be decreased; carbonic anhydrase inhibitors may enhance the adverse/toxic effects of primidone.
Quinidine: Urinary excretion of quinidine may be decreased and effects may be enhanced.
Salicylate use (high dose) may result in carbonic anhydrase inhibitor accumulation and toxicity including CNS depression and metabolic acidosis. Salicylate toxicity might also be enhanced.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Teratogenic in animal studies, however, there are no adequate and well-controlled studies in pregnant women.
LACTATION — Enters breast milk/not recommended (AAP rates "compatible")
DIETARY CONSIDERATIONS — May be taken with food to decrease GI upset. May have additive effects with other folic acid antagonists. Sodium content of 500 mg injection: 47.2 mg (2.05 mEq).
PRICING — (data from drugstore.com)Capsule, 12-hour (Diamox Sequels) 500 mg (60): $169.03
Tablets (AcetaZOLAMIDE) 125 mg (60): $8.98 250 mg (60): $18.99
MONITORING PARAMETERS — Intraocular pressure, potassium, serum bicarbonate; serum electrolytes, periodic CBC with differential; monitor growth in pediatric patients
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms include low blood sugar, tingling of lips and tongue, nausea, yawning, confusion, agitation, tachycardia, sweating, convulsions, stupor, and coma. Hypoglycemia should be managed with 50 mL I.V. dextrose 50% followed immediately with a continuous infusion of 10% dextrose in water (administer at a rate sufficient enough to approach a serum glucose level of 100 mg/dL). The use of corticosteroids to treat the hypoglycemia is controversial, however, the addition of 100 mg of hydrocortisone to the dextrose infusion may prove helpful. In certain instances, hemodialysis may be helpful.
CANADIAN BRAND NAMES — Apo-Acetazolamide®; Diamox®
INTERNATIONAL BRAND NAMES — Acetadiazol (MX); Albox (JP); Apo-Acetazolamide (CA, MY); Azol (TW); Carbinib (PT); Cetamid (PH); Defiltran (DE); Dehydratin (BG); Diamox (AE, AR, AT, AU, BE, BH, BR, CA, CH, CN, CO, CY, DK, EC, EG, ES, FI, FR, GB, HR, ID, IE, IN, IQ, IR, IT, JO, JP, KW, LB, LY, MX, MY, NL, NO, NZ, OM, PH, PY, QA, RU, SA, SE, SG, SY, TH, VE, YE, ZA); Diamox Sustets (CO); Diluran (CZ); Diural (UY); Diuramid (DE, PL); Edemox (ES); Evamox (PK); Genephamide (PE); Glaucomed (CO); Glaupax (CH, DK, HR, IE, JP, NO, TH); Huma-Zolamide (HU); Ledamox (JP); Lediamox (PT); Renamid (HR); Stazol (PY); Uramox (IL)
MECHANISM OF ACTION — 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 to decrease production of aqueous humor; also inhibits carbonic anhydrase in central nervous system to retard abnormal and excessive discharge from CNS neurons
PHARMACODYNAMICS / KINETICS Onset of action: Capsule, extended release: 2 hours; I.V.: 2 minutes Peak effect: Capsule, extended release: 8-12 hours; I.V.: 15 minutes; Tablet: 2-4 hours
Duration: Inhibition of aqueous humor secretion: Capsule, extended release: 18-24 hours; I.V.: 4-5 hours; Tablet: 8-12 hours
Distribution: Erythrocytes, kidneys; blood-brain barrier and placenta; distributes into milk (~30% of plasma concentrations)
Excretion: Urine (70% to 100% as unchanged drug)
PATIENT INFORMATION — Report numbness or tingling of extremities. Do not crush, chew, or swallow contents of long-acting capsule; may be opened and sprinkled on soft food. Ability to perform tasks requiring mental alertness and/or physical coordination may be impaired. Take with food; drug may cause substantial increase in blood glucose in some diabetic patients.
(For additional information see "Acetazolamide: Patient drug information")
PHARMACOLOGIC CATEGORY Anticonvulsant, MiscellaneousCarbonic Anhydrase InhibitorDiuretic, Carbonic Anhydrase InhibitorOphthalmic Agent, Antiglaucoma
DOSING: ADULTS — Note: I.M. administration is not recommended.
Glaucoma: Chronic simple (open-angle): Oral: 250 mg 1-4 times/day or 500 mg extended release capsule twice daily Secondary, acute (closed-angle): I.V.: 250-500 mg, may repeat in 2-4 hours to a maximum of 1 g/day
Edema: Oral, I.V.: 250-375 mg once daily
Epilepsy: Oral: 8-30 mg/kg/day in 1-4 divided doses, not to exceed 1 g/day. Note: Extended release capsule is not recommended for treatment of epilepsy.
Metabolic alkalosis (unlabeled use): I.V. 250 mg every 6 hours for 4 doses or 500 mg single dose; reassess need based upon acid-base status
Mountain sickness: Oral: 250 mg every 8-12 hours (or 500 mg extended release capsules every 12-24 hours). Therapy should begin 24-48 hours before and continue during ascent and for at least 48 hours after arrival at the high altitude. Note: In situations of rapid ascent (such as rescue or military operations), 1000 mg/day is recommended.
Urine alkalinization (unlabeled use): Oral: 5 mg/kg/dose repeated 2-3 times over 24 hours
Respiratory stimulant in COPD (unlabeled use): Oral, I.V.: 250 mg twice daily
DOSING: PEDIATRIC — Note: I.M. administration is not recommended.
(For additional information see "Acetazolamide: Pediatric drug information")
Glaucoma: Oral: 8-30 mg/kg/day or 300-900 mg/m2/day divided every 8 hours I.V.: 20-40 mg/kg/24 hours divided every 6 hours, not to exceed 1 g/day
Edema: Oral, I.V.: 5 mg/kg or 150 mg/m2 once every day
Epilepsy: Oral: Refer to adult dosing.
DOSING: ELDERLY — Oral: Initial: 250 mg once or twice daily; use lowest effective dose possible.
DOSING: RENAL IMPAIRMENT Clcr 10-50 mL/minute: Administer every 12 hours.
Clcr <10 mL/minute: Avoid use (ineffective).
Moderately dialyzable (20% to 50%)
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, extended release: Diamox® Sequels®: 500 mg
Injection, powder for reconstitution: 500 mg
Tablet: 125 mg, 250 mg
DOSAGE FORMS: CONCISE Capsule, extended release: Diamox® Sequels®: 500 mg
Injection, powder for reconstitution: 500 mg
Tablet: 125 mg, 250 mg
GENERIC EQUIVALENT AVAILABLE — Yes: Injection, tablet
ADMINISTRATION Oral: 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.
I.M.: I.M. administration is painful because of the alkaline pH of the drug; use by this route is not recommended.
COMPATIBILITY — Stable in dextran 6% in D5W, dextran 6% in NS, D5LR, D5NS, D51/2NS, D51/4NS, D5W, D10W, LR, NS, 1/2NS.
Y-site administration: Variable (consult detailed reference): Diltiazem, TPN.
Compatibility when admixed: Compatible: Cimetidine, ranitidine. Incompatible: Multivitamins.
USE — Treatment of glaucoma (chronic simple open-angle, secondary glaucoma, preoperatively in acute angle-closure); drug-induced edema or edema due to congestive heart failure (adjunctive therapy); centrencephalic epilepsies (immediate release dosage form); prevention or amelioration of symptoms associated with acute mountain sickness
USE - UNLABELED / INVESTIGATIONAL — Urine alkalinization; respiratory stimulant in COPD; metabolic alkalosis
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined.
Cardiovascular: Flushing
Central nervous system: 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: Appetite decreased, diarrhea, melena, nausea, taste alteration, vomiting
Genitourinary: Crystalluria, glycosuria, hematuria, polyuria, renal failure
Hematologic: Agranulocytosis, aplastic anemia, leukopenia, thrombocytopenia, thrombocytopenic purpura
Hepatic: Cholestatic jaundice, fulminant hepatic necrosis, hepatic insufficiency, liver function tests abnormal
Local: Pain at injection site
Neuromuscular & skeletal: Flaccid paralysis, paresthesia
Ocular: Myopia
Otic: Hearing disturbance, tinnitus
Miscellaneous: Anaphylaxis
CONTRAINDICATIONS — Hypersensitivity to acetazolamide, sulfonamides, or any component of the formulation; hepatic disease or insufficiency; decreased sodium and/or potassium levels; adrenocortical insufficiency, cirrhosis; hyperchloremic acidosis, severe renal disease or dysfunction; severe pulmonary obstruction; long-term use in noncongestive angle-closure glaucoma
WARNINGS / PRECAUTIONS Concerns related to adverse effects: CNS effects: Impairment of mental alertness and/or physical coordination may occur. Sulfa allergy: Chemical similarities are present among sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop diuretics (except ethacrynic acid). Use in patients with sulfonylurea allergy is specifically contraindicated in product labeling, however, a risk of cross-reaction exists in patients with allergy to any of these compounds; avoid use when previous reaction has been severe. Discontinue if signs of hypersensitivity are noted.
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.
Special populations: Elderly: Use with caution in the elderly; may be more sensitive to side effects.
Other warnings/precautions: I.M. administration: Painful because of the alkaline pH of the drug; use by this route is not recommended.
DRUG INTERACTIONS — Inhibits CYP3A4 (weak)
Amphetamines: Urinary excretion of amphetamine may be decreased; magnitude and duration of effects may be enhanced.
Carbamazepine: May increase serum concentrations of carbamazepine.
Cyclosporine trough concentrations may be increased resulting in possible nephrotoxicity and neurotoxicity.
Flecainide: May decrease excretion of flecainide.
Lithium: Serum concentrations may be decreased by acetazolamide; monitor.
Memantine: May decrease excretion of memantine.
Methenamine: Urinary antiseptic effect may be prevented by acetazolamide.
Phenytoin: Serum concentrations of phenytoin may be increased; incidence of osteomalacia may be enhanced or increased in patients on chronic phenytoin therapy.
Primidone serum concentrations may be decreased; carbonic anhydrase inhibitors may enhance the adverse/toxic effects of primidone.
Quinidine: Urinary excretion of quinidine may be decreased and effects may be enhanced.
Salicylate use (high dose) may result in carbonic anhydrase inhibitor accumulation and toxicity including CNS depression and metabolic acidosis. Salicylate toxicity might also be enhanced.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Teratogenic in animal studies, however, there are no adequate and well-controlled studies in pregnant women.
LACTATION — Enters breast milk/not recommended (AAP rates "compatible")
DIETARY CONSIDERATIONS — May be taken with food to decrease GI upset. May have additive effects with other folic acid antagonists. Sodium content of 500 mg injection: 47.2 mg (2.05 mEq).
PRICING — (data from drugstore.com)Capsule, 12-hour (Diamox Sequels) 500 mg (60): $169.03
Tablets (AcetaZOLAMIDE) 125 mg (60): $8.98 250 mg (60): $18.99
MONITORING PARAMETERS — Intraocular pressure, potassium, serum bicarbonate; serum electrolytes, periodic CBC with differential; monitor growth in pediatric patients
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms include low blood sugar, tingling of lips and tongue, nausea, yawning, confusion, agitation, tachycardia, sweating, convulsions, stupor, and coma. Hypoglycemia should be managed with 50 mL I.V. dextrose 50% followed immediately with a continuous infusion of 10% dextrose in water (administer at a rate sufficient enough to approach a serum glucose level of 100 mg/dL). The use of corticosteroids to treat the hypoglycemia is controversial, however, the addition of 100 mg of hydrocortisone to the dextrose infusion may prove helpful. In certain instances, hemodialysis may be helpful.
CANADIAN BRAND NAMES — Apo-Acetazolamide®; Diamox®
INTERNATIONAL BRAND NAMES — Acetadiazol (MX); Albox (JP); Apo-Acetazolamide (CA, MY); Azol (TW); Carbinib (PT); Cetamid (PH); Defiltran (DE); Dehydratin (BG); Diamox (AE, AR, AT, AU, BE, BH, BR, CA, CH, CN, CO, CY, DK, EC, EG, ES, FI, FR, GB, HR, ID, IE, IN, IQ, IR, IT, JO, JP, KW, LB, LY, MX, MY, NL, NO, NZ, OM, PH, PY, QA, RU, SA, SE, SG, SY, TH, VE, YE, ZA); Diamox Sustets (CO); Diluran (CZ); Diural (UY); Diuramid (DE, PL); Edemox (ES); Evamox (PK); Genephamide (PE); Glaucomed (CO); Glaupax (CH, DK, HR, IE, JP, NO, TH); Huma-Zolamide (HU); Ledamox (JP); Lediamox (PT); Renamid (HR); Stazol (PY); Uramox (IL)
MECHANISM OF ACTION — 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 to decrease production of aqueous humor; also inhibits carbonic anhydrase in central nervous system to retard abnormal and excessive discharge from CNS neurons
PHARMACODYNAMICS / KINETICS Onset of action: Capsule, extended release: 2 hours; I.V.: 2 minutes Peak effect: Capsule, extended release: 8-12 hours; I.V.: 15 minutes; Tablet: 2-4 hours
Duration: Inhibition of aqueous humor secretion: Capsule, extended release: 18-24 hours; I.V.: 4-5 hours; Tablet: 8-12 hours
Distribution: Erythrocytes, kidneys; blood-brain barrier and placenta; distributes into milk (~30% of plasma concentrations)
Excretion: Urine (70% to 100% as unchanged drug)
PATIENT INFORMATION — Report numbness or tingling of extremities. Do not crush, chew, or swallow contents of long-acting capsule; may be opened and sprinkled on soft food. Ability to perform tasks requiring mental alertness and/or physical coordination may be impaired. Take with food; drug may cause substantial increase in blood glucose in some diabetic patients.
(For additional information see "Acetazolamide: Patient drug information")
Subscribe to:
Posts (Atom)