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Acetazolamide

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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.

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