Clinical Conundrum: Why is my patient on a thiazide-type drug along with a loop diuretic?
Background:
Combination therapy most likely due to refractory edema which is defined as edema that is refractory to typically effective doses of loop diuretics.
There are several potential causes such as noncompliance to medications, inadequate diuretic dose, or frequency, decreased intestinal absorption of oral meds, decreased diuretic tubular secretion, excess sodium intake, concomitant administration of other drugs that can interfere with action of the diuretic.
The addition of a thiazide medication like metolazone to a loop diuretic can overcome refractory edema by blocking the sodium reabsorption in multiple sites in the nephron leading to enhanced sodium excretion.
Answer:
Many providers use metolazone as the oral thiazide diuretic of choice in patients with refractory edema and have advanced chronic kidney disease (GFR < 20 mL/min) since other thiazide-type drugs were thought to be ineffective in this setting.
However, there is no convincing evidence that metolazone is superior to other thiazides in comparable doses such as chlorthalidone and indapamide which have the advantage of once-daily dosing.
Administration timing of the thiazide-diuretic is important, which should be given 30 to 60 minutes prior to administration to the loop diuretic.
References:
High dosage metolazone in chronic renal failure. Br Med J. 1972;4(5834):196.
Diuretic drugs and the treatment of edema: from clinic to bench and back again. Am J Kidney Dis. 1994;23(5):623.
Diuretic Resistance. Am J Kidney Dis. 2017;69(1):136.
Written by:
Joanne C. Routsolias, PharmD, RN, BCPS
Clinical PharmD Specialist - Emergency Medicine/Toxicology
Cook County Health