acetazolamide (Diamox Sequels)

Dosing and uses of Diamox Sequels (acetazolamide)

• Adult
• Pediatric
• Geriatric

 

Adult dosage forms and strengths

tablet

• 125mg
• 250mg

powder for injection

• 500mg

capsule, extended-release

• 500mg

 

Glaucoma

Closed-angle (acute congestive) glaucoma

• 500 mg PO/IV, followed by 125-250 mg PO q4hr
• Sustained-release: 500 mg PO q12hr

Open-angle (chronic simple) glaucoma

• 250 mg-1 g PO/IV qDay or divided q6-12hr
• Sustained-release: 500 mg PO q12hr

Secondary glaucoma

• 500 mg PO/IV, followed by 125-250 mg PO q4hr
• Sustained-release: 500 mg PO q12hr

 

Acute Altitude Sickness

Immediate release: 500-1000 mg/day PO divided q8-12hr

Extended release: 500-1000 mg PO q12-24hr

Dosing considerations

• Start 24-48 hours before ascent and continue for 48 hours at high altitude or longer, to control symptoms if necessary

 

Congestive Heart Failure

CHF-associated edema

250-375 mg (5 mg/kg) PO qAm

 

Seizure

8-30 mg/kg/day PO qDay or divided q12hr

 

Drug-induced Edema

250-375 mg PO/IV qDay

Dosing considerations

• Do not increase dose if edema fails to decrease following an initial response; allow instead kidney recovery by skipping medication for a day; best results obtained when given on alternate days or for 2 days followed by a day of rest

 

Epilepsy

Tablet: 8-30 mg/kg/day PO qDay, OR divided q6-12 hr; not to exceed 30 mg/kg/day or 1 g/day

Extended-release capsule: Not recommended

 

Dosing Modifications

Renal impairment

• CrCl 10-50 mL/min: Administer no more frequently than q12hr
• CrCl <10 mL/min: Ineffective (avoid use)
• Hemodialysis: 20-50% dialyzable
• Peritoneal dialysis: Dose adjustment not necessary

 

Pediatric dosage forms and strengths

tablet

• 125mg
• 250mg

powder for injection

• 500mg

capsule, extended-release

• 500mg

 

Epilepsy

<12 years

• Safety and efficacy not established

>12 years

• Tablet: 8-30 mg/kg/day PO qDay or divided q6-12 hr; not to exceed 30 mg/kg/day or 1 g/day
• Extended-release capsule: Not recommended

 

Acute Altitude Sickness

<12 years

• Safety and efficacy not established

>12 years

• Immediate release: 500-1000 mg/day PO divided q8-12hr
• Extended release: 500-1000 mg PO q12-24hr

Dosing considerations

• Start 24-48 hr before ascent and continue for 48 hr at high altitude to control symptoms, if necessary

 

Geriatric dosage forms and strengths

250 mg PO qDay or q12hr; use lowest effective dose possible

 

Diamox Sequels (acetazolamide) adverse (side) effects

Frequency not defined

Confusion

Convulsions

Drowsiness

Flaccid paralysis

Malaise

Paresthesias

Photosensitivity

Urticaria

Anorexia

Diarrhea

Metallic taste

Nausea

Vomiting

Hepatic disease

Aplastic anemia

Agranulocytosis

Leukopenia

Thrombocytopenia

Thrombocytopenic purpura

Melena

Acidosis

Electrolyte imbalance

Muscle weakness

Hematuria

Polyuria

Glycosuria

Hearing dysfunction or tinnitus

Sulfonamide type reactions

 

Warnings

Contraindications

Hypokalemia

Hyponatremia

Hyperchloremic acidosis

Hypersensitivity to acetazolamide or sulfa

Liver disease

Severe renal disease or dysfunction

Long term use in noncongestive angle-closure glaucoma

Cirrhosis

Long-term administration in patients with chronic, noncongestive angle-closure glaucoma

 

Cautions

Use caution in COPD, emphysema, and concomitant high-dose aspirin

Use caution in diabetes, respiratory acidosis, and hepatic impairment

Adverse drug reactions common to sulfonamide derivatives; Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN) may occur

May impair alertness and/or physical coordination

FDA-approved product labeling for many medications have included a broad contraindication in patients with a prior allregic reaction to sulfonamides; however, recent studies have suggested that crossreactivity between antibiotic sulfonamides and nonantibiotic sulfonamides is unlikely to occur

May impair alertness and/or physical coordination

Severe adverse effects including tachypnea, anorexia, coma, lethargy, and death reported with high-dose aspirin; use caution or avoid administration

Increasing dose does not increase diuresis; may instead increase the incidence of paresthesia and/or drowsiness

IM administration not recommended due to alkaline pH, which may cause pain

 

Pregnancy and lactation

Pregnancy category: C

Lactation: Enters breast milk; not recommended

 

Pregnancy categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

 

Pharmacology of Diamox Sequels (acetazolamide)

Mechanism of action

Carbonic anhydrase inhibitor that decreases rate of aqueous humor formation, in that way decreasing intraocular pressure

Inhibits H+ ion excretion in renal tubule, increasing sodium, potassium, bicarbonate, and water excretion and producing alkaline diuresis

Inhibits carbonic anhydrase in CNS, which in turn decreases abnormal and excessive discharge from the CNS neurons

 

Absorption

Bioavailability: Rapidly absorbed orally

Tablet

• Onset: 1-1.5 hr
• Duration: 8-12 hr
• Peak plasma time: 1-4 hr

Sustained-release

• Onset: 2 hr
• Duration: 18-24 hr
• Peak plasma time: 8-18 hr

IV

• Onset: 5-10 min
• Duration: 4-5 hr
• Peak plasma time: 15 min

 

Distribution

Protein bound: 70-90%

Vd: 0.2 L/kg

 

Metabolism

Metabolism: None

 

Elimination

Half-life: 2-4 hr (tablet)

Dialyzable: Yes (hemodialysis)

Excretion: Urine 90%

 

Administration

IV Incompatibilities

Additive: Multivitamins

Y-site: Diltiazem(?), multivitamins

 

IV Compatibilities

Solution: Compatible with most common solvents

Additive: Cimetidine, ranitidine

 

IV Preparation

Standard diluent: 500 mg/50 mL D5W

Minimum volume: 50 mL D5W

 

IV Administration

IV push: 100-500 mg/min

Infusion: 4-8 hr

 

Storage

Store intact vials at room temperature

May store reconstituted solution in refrigerator for 3 days or at room temperature for 12 hr