Amiloride may be used in combination with a thiazide diuretic for treatment of high blood pressure or (less commonly) in combination with a loop diuretic for treatment of
heart failure. The potassium-sparing effects of amiloride offset the low blood potassium (
hypokalemia) that is often induced by thiazides or loop diuretics, which is of particular importance in people for whom maintaining a normal level of potassium is critically important. For people with resistant hypertension, already taking a thiazide diuretic, an
angiotensin converting enzyme inhibitor (ACE-i) or an
angiotensin II receptor blocker (ARB), and a
calcium channel blocker, the addition of amiloride (or
spironolactone) was better at reducing blood pressure than adding a beta-blocker (
bisoprolol) or an
alpha-1 blocker (
doxazosin). When combined with hydrochlorothiazide, the addition of amiloride had positive effects on blood pressure and blood sugar tolerance. Amiloride may therefore be useful for preventing the metabolic side effects of thiazide diuretics, allowing for the use of higher thiazide doses (in line with how they were originally studied). Amiloride is the treatment of choice for
Liddle phenotype, which is characterized by high blood pressure, low blood potassium, and metabolic alkalosis in conjunction with a low plasma renin activity and a low aldosterone. Some people with the Liddle phenotype have
Liddle syndrome, which involves a genetic mutation resulting in upregulation of the epithelial sodium channel (ENaC), located in the apical membrane of polarized epithelial cells in the late distal tubule and
collecting duct of the kidney. Because Liddle phenotype usually involves an upregulation of ENaC channels, leading to retention of sodium and water and to hypokalemia, amiloride is useful as an ENaC channel inhibitor due to its
promotion of sodium excretion and its potassium-sparing effects, restoring potassium to normal levels. Amiloride can be used as a monotherapy (single-drug therapy) or an adjunctive therapy alongside other diuretics (e.g.
hydrochlorothiazide,
furosemide) for the treatment of
ascites and
edema (swelling) due to
cirrhosis of the liver. The 2012 clinical practice guidelines by the
American Association for the Study of Liver Diseases (AASLD) states that amiloride can be used to treat ascites in place of
spironolactone if it isn't tolerated (e.g. due to the side effect of
gynecomastia), though amiloride isn't a preferred drug due to cost and lack of efficacy.
Specific populations Diabetics People with diabetes are at higher risk for
kidney problems, which increases their risk for hyperkalemia (high blood potassium). The use of amiloride in people with diabetes requires careful potassium and kidney function monitoring to prevent toxicity. Amiloride must be discontinued for at least 3 days prior to glucose tolerance testing, due to the risk for fatal hyperkalemia.
Pregnancy Data from the use of amiloride in animals suggests that it does not pose a risk to the developing fetus. However, when used in combination with the drug
acetazolamide during the process of
organ formation, amiloride increases the risk for kidney and ureter abnormalities. Limited human data from use during pregnancy suggests an association with a specific
congenital penis abnormality if taken during the first trimester, as well as a risk for mild
intrauterine growth restriction if taken throughout pregnancy. ==Contraindications==