NEODOSE

INDICATIONS

• Chronic lung disease, adjunct: Diuretic that may also improve pulmonary function. Based on results from a systematic review of the use of furosemide in infants with (or developing) chronic lung disease (CLD), furosemide was associated with no or inconsistent effects on lung function in preterm infants less than 3 weeks of age. For preterm infants greater than 3 weeks of age with CLD, single IV doses were associated with short-term (less than 1 hour) improvement in lung compliance and airway resistance. Infants receiving chronic diuretic therapy had improved oxygenation and lung compliance. There are no data to support the routine or sustained use of loop diuretics based on duration of ventilatory support, duration of hospitalization, long-term outcomes, or survival in infants with CLD.
• Heart Failure: In neonates with pulmonary hypertension, supportive care with diuretics may be used cautiously for signs of right-sided heart failure.
• Posthemorrhagic ventricular dilation (PHVD), adjunct; Prevention of shunt placement:Use of acetazolamide and furosemide in preterm infants with PHVD was associated with a higher rate of shunt placement, death, and increased neurological morbidity as compared to standard therapy alone, in a multicenter, randomized, controlled trial (n=177). Infants less than 3 months beyond the expected date of delivery and with a ventricular width more than 4 mm above the 97th percentile after intraventricular hemorrhage received either standard therapy plus acetazolamide 100 mg/kg daily and furosemide 1 mg/kg daily (n=88) or standard therapy alone (n=89). Mean gestational age was 28.5 weeks and median postnatal age was 23.5 days in the drug therapy group. Median treatment duration of acetazolamide was 35 days. Assessments at 1 year showed that death or shunt placement had occurred in 56 infants (63.3%) in the drug therapy group and in 46 (52.2%) allocated to standard therapy (11.1% (CI, -3.2% to 25.2%; p=0.15). Adverse effects were reported in 38 infants; 23 of whom required permanent discontinuation of drug therapy. In a small cohort study, 9 of 10 preterm infants with raised intracranial hypertension secondary to PVHD treated with acetazolamide and furosemide avoided the placement of ventriculoperitoneal shunt; in comparison, 3 of 6 patients who received serial lumbar puncture avoid shut placement. Acetazolamide was started at 20 mg/kg/day and increased by 10 mg/kg up to 100 mg/kg/day in 3 divided doses administered orally or if necessary, IV; dose of furosemide was 1 mg/kg daily orally or IV. Mean gestational age was 28.4 weeks. Limited use of acetazolamide may be warranted in infants with PVHD and raised intracranial hypertension based on the findings of Kennedy et al, 2001.

CONTRAINDICATIONS

• Anuria
• History of hypersensitivity to furosemide.

PRECAUTIONS

• Cardiovascular:
  • Increased risk of persistent patent ductus arteriosis when administrated to premature infants during first week of life.
• Concomitant Use:
  • Avoid aminoglycosides.
  • Ethacrynic acid not recommended.
• Endocrine & Metabolic:
  • Preexisting electrolyte depletion should be corrected prior to treatment.
  • Excessive diuresis may cause dehydration and blood volume reduction with circulatory collapse and possibly vascular thrombosis and embolism.
  • Electrolyte imbalance, including hyponatremia, hypochloremic alkalosis, hypokalemia, hypomagnesemia, and hypocalcemia, may occur especially in patients receiving higher doses and a restricted salt intake; monitoring recommended.
  • Hypokalemia has been reported, especially with brisk diuresis, inadequate electrolyte intake, cirrhosis, or concomitant use with corticosteroids, ACTH, large amounts of licorice, or prolonged use of laxatives.
  • Blood glucose increases, alterations in glucose tolerance tests, or precipitation of diabetes have been reported.
  • Asymptomatic hyperuricemia or gout may occur.
• Hematologic:
  • Blood dyscrasias may occur; monitoring recommended.
• Hepatic:
  • Hepatic damage may occur; monitoring recommended.
  • Patients with preexisting hepatic cirrhosis and ascites may experience precipitated hepatic coma with sudden fluid or electrolyte alteration; strict monitoring recommended.
  • Not recommended in patients with preexisting hepatic coma until basic condition is improved.
• Immunologic:
  • Patients with preexisting systemic lupus erythematosus may be at risk for exacerbation or activation.
  • Patients with sulfonamide allergy are at increased risk of furosemide allergy.
• Otic:
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  • Hearing loss has been associated with furosemide injection in neonates.
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• Renal:
  • Renal damage may occur; monitoring recommended.
  • Use caution in patients with preexisting severe progressive renal disease; discontinue if azotemia and oliguria worsen.
  • Nephrocalcinosis or nephrolithiasis may be precipitated in premature infants and may also occur in children under 4 years without prematurity receiving chronic therapy; monitoring recommended.
  • Severe urinary retention increases risk of acute urinary retention particularly during initial stages of treatment; monitoring recommended.
  • Patients at high-risk for radiocontrast nephropathy may experience higher incidence of renal deterioration.
  • Patients with hypoproteinemia (associated with nephrotic syndrome) may experience reduced efficacy and increased risk of ototoxicity.

ADVERSE EFFECTS

Furosemide therapy may lead to increased hyponatremia and a significant rise in serum creatinine in patients receiving indomethacin for PDA closure.

• Otic: After adjusting for risk factors and severity of illness, no association was demonstrated between prolonged furosemide (at least 28 days duration) and hearing screen failure in a cohort of premature infants from the Pediatrix Medical Group. The absolute difference in hearing screen failure between those exposed (n=1020) and those not exposed (n=790) to furosemide was 3% (95% CI, -0.2% to 6.2%).
• Renal: Nephrocalcinosis and nephrolithiasis may occur due to high urinary calcium excretion. This has been reported mainly in premature infants and a cumulative dose of 10 mg/kg or greater was associated with an increased risk. Cases have also occurred in infants with no history of prematurity; monitoring recommended. Hypercalciuria and development of bone demineralization and renal calculi occur with longterm therapy. May displace bilirubin from albumin binding sites when given in high doses or for prolonged periods. Cholestatic jaundice and cholelithiasis have also been reported with loop diuretics (mainly in preterm infants receiving long-term TPN and furosemide therapy..

ADMINISTRATION

Administer a 2 to 10 mg/mL concentration of furosemide over 15 to 30 minutes.

BLACK BOX WARNING

Furosemide is a potent diuretic which, if given in excessive amounts, can lead to profound diuresis with water and electrolyte depletion. Therefore, careful medical supervision is required and dose and dose schedule must be adjusted to the individual patient’s needs.

MONITORING

Monitor serum and urine electrolytes and renal function periodically during therapy. Consider performing renal ultrasonography in premature infants as furosemide may precipitate nephrocalcinosis/nephrolithiasis. Follow serum potassium levels closely at initiation, in patients receiving concomitant diuretics or digoxin, and during long-term therapy. Monitor urine output and weight changes. Monitor for signs/symptoms of fluid/electrolyte imbalance.