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Furosemide


Dose & administration
1-2 mg/kg/dose. Intravenous injection or oral administration, intermittently or on a regular basis once or twice per 24 hours.
Can be given as intravenous infusion from 0.1-0.2 mg/kg/h. If oliguria persists, the infusion rate may be increased to 0.4 mg/kg/h.
Lower and less frequent doses should be considered to preterm infants

Indications
Need to increase diuresis. May be used in various conditions complicated by fluid retention and/or low urine output.

Contraindications and special considerations
Use cautiously in extremely preterm infants, in infants with renal impairment, in infants with severe jaundice and in infants with hyponatremia and/or hypokalemia.
Furosemide injection solution has an alcalotic pH of ~9 and should not be mixed with acidic solutions with pH<5.5, as furosemide may precipitate.

Adverse effects
Electrolyte disturbances including hypochloremic alkalosis
Nephrocalcinosis
Risk of bone demineralization
Hyperuricemia
Ototoxicity
Cholestatic jaundice/cholelithiasis
Drug fever
Skin reactions including Stevens-Johnson syndrome

Pharmacological  aspects
Furosemide acts on the loop of Henley with a rapid onset. The chloride site of the Na/K/Cl-channel is blocked and sodium reabsorption is inhibited, leading to diuresis. Chloride site blockade leads to increased excretion of potassium and chloride, and reduced absorption of calcium and magnesium. Repeated administration leads to pharmacologic tolerance.

Gastric pH, delayed gastric emptying and slower intestinal transit time influence absorption of diuretics in infants.

Renal and hepatic pathways eliminate furosemide. In neonates, non-renal clearance is limited, but non-renal clearance increases during childhood. Half times in newborn infants varies but extends over 8-24 hours. Preterm infants have longer half times than term infants, and clearance improves with postnatal age.

Furosemide displaces other drugs bound to albumin, and critically ill infants may risk increased levels of free bilirubin.

References
Segar. Neonatal Diuretic Therapy: Furosemide, Thiazides, and Spironolactone. Clin Perinatol 2012;39:209–220. PMID 22341547.
Pacifici.Clinical pharmacology of furosemide in neonates: a Review. Pharmaceuticals (Basel). 2013 Sep 5;6(9):1094-129. PMID 24276421.
Pacifici. Clinical Pharmacology of the Loop Diuretics Furosemide and Bumetanide in Neonates and Infants. Pediatr Drugs 2012;14:233-246. PMID 22702741.
van der Vorst. Diuretics in Pediatrics. Pediatr Drugs 2006;8:245-264. PMID 16898855.

Document version history
Created 2016-05-15 / Stefan Johansson
Revised 2016-05-25 / Stefan Johansson



Recommended Comments

I wonder if it will be useful to add incompatibility clause:

Furosemide has a pH of 8.7-9.3 and therefore should not
be mixed with acidic solutions of pH <5.5.
This includes glucose 5% and 10%, Ambisome®,
caffeine, ciprofloxacin, dobutamine, dopamine,
erythromycin, esmolol, fluconazole, gentamicin,
midazolam, morphine,

  • Upvote 1

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Hi Stefan,

maybe you would like to add this (excellent) review too:

Pacifici GM: Clinical Pharmacology of Furosemide in Neonates: A Review. Pharmaceuticals (Basel) 2013;6:1094–1129.

There is some growing evidence of concerns about the furosemid interaction with chondrocytes in the growth plate leading to growth restriction:
 
1.
Bush PG, Pritchard M, Loqman MY, Damron TA, Hall AC: A key role for membrane transporter NKCC1 in mediating chondrocyte volume increase in the mammalian growth plate. J Bone Miner Res 2010 Jul;25:1594–1603.
2.
Iwamoto LM, Fujiwara N, Nakamura KT, Wada RK: Na-K-2Cl cotransporter inhibition impairs human lung cellular proliferation. Am J Physiol Lung Cell Mol Physiol 2004 Sep;287:L510–514.
3.
Koo WW, Guan ZP, Tsang RC, Laskarzewski P, Neumann V: Growth failure and decreased bone mineral of newborn rats with chronic furosemide therapy. Pediatr Res 1986 Jan;20:74–78.

Greetings from the rainy south side of the town :-)

Dirk

  • Upvote 2

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@wackdi Great feedback, I add the review you suggest, it is great!
The concerns about interactions with chondrocytes is also very interesting and is def one more reason to be restrictive with the use of furosemide.
BTW, thanks for commenting, this is exactly how we want this Pharmacopedia to evolve, like an interactive NeoFax :) 

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