Amiloride is a potassium-sparing diuretic used in the therapy of edema often in combination with thiazide diuretics. Amiloride has been linked to rare cases of clinically apparent drug induced liver disease.
Amiloride (a mil' oh ride) is a pyrazinoylguanidine derivative that acts on the sodium channels of renal epithelial cells causing an increase in sodium excretion with little or no effect on potassium excretion, thus accounting for its potassium-sparing characteristics. Amiloride is similar in action to triamterene, but differs in chemical structure. Amiloride was approved for use in the United States in 1986, but is not widely used. Amiloride is available in 5 mg tablets in generic forms and under the brand name of Midamor. The typical dose of amiloride is 5 to 20 mg in one or two doses daily. Amiloride causes only a modest diuresis and it is often used in combination with a thiazide diuretic (such as hydrochlorothiazide: Moduretic), which takes advantage of it potassium-sparing characteristics to offset the potassium-wasting characteristics of the thiazides. The major side effects of amiloride include hyperkalemia, headache, dizziness, gastrointestinal upset and rash.
Amiloride therapy has not been associated with serum aminotransferase elevations. Idiosyncratic, clinically apparent liver injury from amiloride is rare, but several instances have been reported as isolated case reports in which the combination of amiloride with hydrochlorothiazide was used (Case 1). The numbers of cases have been too few to characterize the clinical features, but the latency to onset was ranged from 2 to 12 months and the pattern of injury either hepatocellular or mixed. Immunoallergic features and autoantibodies have not been associated with the liver injury from amiloride.
Likelihood score: D (possible rare cause of liver injury).
Mechanism of Injury
The mechanism of amiloride hepatic injury is unknown, but is likely due to metabolic idiosyncrasy.
Outcome and Management
The rare instances of clinically apparent liver injury due to amiloride/hydrochlorothiazide combinations have been associated with jaundice and at least one case resulted in cirrhosis and ultimately death from liver disease. There is unlikely to be cross reactivity to the liver injury with other potassium-sparing diuretics, which have quite different chemical structures.
|Medication:||Amiloride (2.5 mg) and hydrochlorothiazide (25 mg daily)|
|Severity:||3+ (jaundice, hospitalization)|
|Recovery:||Incomplete at 4 months|
|Time After Starting||Time After Stopping||ALT (U/L)||Alk P (U/L)||Bilirubin* (mg/dL)||Other|
|8 weeks||0||2930||494||11.1||Diuretics stopped|
|9 weeks||1 week||1466||351||18.5||Liver biopsy|
|11 weeks||3 weeks||697||309||28.3||Prednisolone started|
|5 months||3 months||29||176||1.5||Prednisolone stopped|
|6 months||4 months||196||225||1.5|
|DRUG||CAS REGISTRY NUMBER||MOLECULAR FORMULA||STRUCTURE|
Top of page