Amiloride
Amiloride is a potassium-sparing diuretic used for hypertension and oedema, primarily in fixed-dose combinations with hydrochlorothiazide to offset thiazide-induced hypokalaemia. It works through a different mechanism than spironolactone, blocking distal-tubule sodium channels directly.
- Chemical formula
- C6H8ClN7O
- CAS number
- 2609-46-3
- ATC code
- C03DB01
- Molecular weight
- 229.63 g/mol
- Drug class
- Potassium-sparing diuretic
- Also known as
- Midamor, Modamide
What is it?
Amiloride is a potassium-sparing diuretic in clinical use since 1967, marketed as Midamor (US) and Modamide (some European markets). Authorised generic amiloride is widely available, and the molecule is also one of the components of common fixed-dose combinations such as Moduretic (amiloride + hydrochlorothiazide). Most current use of amiloride is in these combinations rather than as monotherapy, where it counteracts thiazide-induced potassium loss.
Mechanism of action
Amiloride blocks the epithelial sodium channel (ENaC) in the distal convoluted tubule and collecting duct of the kidney, reducing sodium reabsorption and indirectly decreasing potassium and hydrogen ion excretion. This mechanism produces a mild diuretic effect with potassium-sparing action — distinct from spironolactone, which acts by aldosterone receptor antagonism. The mechanism is independent of aldosterone levels, making amiloride useful in hyperaldosterone states and in patients who do not tolerate spironolactone.
Pharmacokinetics
Amiloride has variable oral bioavailability of ~50% with peak plasma at 3–4 hours. Onset of diuresis is within 2 hours, peak effect at 6–10 hours, and duration ~24 hours, supporting once-daily dosing. The drug is not metabolised significantly and is excreted unchanged in urine, making renal function a key determinant of effect and toxicity. Reduced renal function increases the risk of hyperkalaemia.
Indications
Amiloride is approved for hypertension (typically in combination with thiazides), oedema in heart failure or hepatic cirrhosis (in combination), and primary hyperaldosteronism (Liddle syndrome and pseudohyperaldosteronism). According to current hypertension guidelines, amiloride is most useful as a low-dose addition to thiazides to prevent hypokalaemia rather than as monotherapy, with spironolactone preferred when significant aldosterone antagonism is desired (heart failure, resistant hypertension).
Safety profile
Common adverse effects include hyperkalaemia (the main risk), hyponatraemia, dehydration and gastrointestinal upset. Unlike spironolactone, amiloride does not cause gynaecomastia or sexual side effects because it does not interact with sex steroid receptors. Hyperkalaemia risk is amplified by ACE inhibitors, ARBs, NSAIDs, potassium supplements and renal impairment. According to the prescribing information, serum potassium and renal function require periodic monitoring, particularly when amiloride is combined with ACE inhibitors or ARBs.
Products containing this ingredient
Frequently asked questions
How does amiloride differ from spironolactone? ▾
Both are potassium-sparing diuretics, but they act differently. Amiloride directly blocks the epithelial sodium channel, independent of aldosterone, while spironolactone blocks the aldosterone receptor. Practically, amiloride does not cause gynaecomastia or sexual side effects, and is preferred when these are concerns. Spironolactone is preferred when significant aldosterone antagonism is needed (heart failure, resistant hypertension).
Why is amiloride often combined with hydrochlorothiazide? ▾
Hydrochlorothiazide promotes potassium loss; amiloride conserves potassium. The combination (Moduretic, co-amilozide) provides effective blood-pressure reduction while minimising hypokalaemia, allowing low effective doses of each. According to current practice, this is one of the most commonly used potassium-sparing combinations in older adults with hypertension.
What lab tests are needed on amiloride? ▾
Serum potassium and creatinine are checked at baseline, 1–2 weeks after starting or any dose increase, and periodically thereafter. According to the prescribing information, hyperkalaemia is the main risk and is amplified by ACE inhibitors, ARBs, NSAIDs and renal impairment. Persistent hyperkalaemia warrants dose reduction or alternative therapy.
The information on this website is provided for reference and educational purposes only. It does not replace consultation with a qualified healthcare professional.