acetazolamide

Acetazolamide

Dose: 5 mg/kg/dose IV, PO (not IM)

Frequency: Q 6 or 8 hours

Comments: Acetazolamide is a carbonic anhydrase inhibitor. When the enzyme is inhibited, sodium ions are not reabsorbed and are lost in the urine as sodium bicarbonate. Additionally, large amounts of potassium are also lost. Although it is not an effective diuretic in the newborn, it has been used to treat newborns with hydrocephalus. A recent RCT however found it did not prevent placement of VP shunts and may be associated with a worse developmental outcome. Use of the drug causes a decrease in CSF formation. It also appears to have an effect upon seizures both directly and as a consequence of a subsequent metabolic acidosis. Finally, acetazolamide decreases the formation of aqueous humor in the eye. The doses used in infants have varied. Because of the metabolic problems, it might be more useful to start with a lower dose, 5 mg/kg, and increase the dose if the infant tolerates it. Though 25 mg/kg/day is the recommended maximum, Shinar (J Pediatr 1985; 107:31) reported halting the progression of hydrocephalus in 50% of a select population using a 100 mg/kg/day dose of acetazolamide and 1 mg/kg/day of furosemide, though Kennedy (Pediatr 2001; 108:597-607) found no benefit when using this regimen. Further comments of acetazolamide.

Toxicity: In infants, hyperchloremic metabolic acidosis, electrolyte disturbance, poor feeding, osteopenia, hypercalciuria and nephrocalcinosis, diarrhea, and vomiting have been reported. Cowan (Acta Paediatr Scand 1991; 80:22-27) reported increased cerebral blood flow and increased intracranial pressure following IV administration. It has the potential to impair CNS autoregulation. Adverse reactions during short term therapy in adults are minimal and include loss of appetite, polyuria, and confusion. With long term therapy in adults, metabolic acidosis and hypokalemia are the most likely problems. Rarely, melena, hematuria, glycosuria, hepatic insufficiency, flaccid paralysis, and convulsions have been reported. Adverse reactions common to sulfonamides are possible but have not been reported in newborns. They include anaphylaxis, fever, rash (Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme), renal calculus, hemolytic anemia, thrombocytopenic purpura, leukopenia, pancytopenia, and agranulocytosis

Preparation:
IV: Acetazolamide (Diamox) is available in a 500 mg vial (500 mg/10 ml). Add 10 ml of SWFI to the vial to reconstitute. The resulting concentration is 50 mg/ml. Stable 24 hours after vial is entered if refrigerated.

PO: An oral formulation of acetazolamide (Diamox) can be prepared with a concentration of 12.5 mg/ml. Add one (1) 250 mg tablet in 10 ml of hot water. Add 10 ml of 70% sorbitol (pH = 4 to 5). Transfer to an amber bottle. Stable for 3 months at room temperature (Facts and Comparisons, Inc. Drug Facts and Comparisons. Olin, B.R. ed. St. Louis, MO: Facts and Comparisons, Inc; 1994, page 139c). Do not use with milk or fruit juice.

Compatibility: Compatible with D5W, D10W, LR, NS, 1/2 NS, and ranitidine. Incompatible with multivitamin preparations for TPN. No information available on filter other drugs.

**Acetazolamide 50 mg/ml concentration and an IV dose of 5 mg/kg**
Weight	Dose (ml)	Weight	Dose (ml)
500	0.05	3000	0.30
750	0.08	3250	0.33
1000	0.10	3500	0.35
1250	0.13	3750	0.38
1500	0.15	4000	0.40
1750	0.18	4250	0.43
2000	0.20	4500	0.45
2250	0.23	4750	0.48
2500	0.25	5000	0.50
2750	0.28	5250	0.53

**Acetazolamide 12.5 mg/ml concentration and a PO dose of 5 mg/kg**
Weight	Dose (ml)	Weight	Dose (ml)
500	0.20	3000	1.20
750	0.30	3250	1.30
1000	0.40	3500	1.40
1250	0.50	3750	1.50
1500	0.60	4000	1.60
1750	0.70	4250	1.70
2000	0.80	4500	1.80
2250	0.90	4750	1.90
2500	1.00	5000	2.00
2750	1.10	5250	2.10

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