Usage
Amiloride is a potassium-sparing diuretic prescribed for:
- Hypertension: Used alone or with other antihypertensives to lower blood pressure.
- Edema (Fluid Retention): Associated with congestive heart failure, hepatic cirrhosis with ascites, and other conditions.
- Thiazide-induced Hypokalemia: To prevent or treat low potassium levels caused by thiazide diuretics.
Pharmacological Classification: Potassium-sparing diuretic.
Mechanism of Action: Amiloride blocks epithelial sodium channels (ENaCs) in the distal convoluted tubule and collecting duct of the nephron, inhibiting sodium reabsorption. This leads to increased sodium excretion, along with water, while minimizing potassium loss.
Alternate Names
- Generic: Amiloride hydrochloride
- Brand Names: Midamor, Moduretic (combined with hydrochlorothiazide)
How It Works
Pharmacodynamics: By blocking ENaCs, amiloride reduces sodium reabsorption in the distal nephron, producing a mild diuresis and lowering blood pressure. Its potassium-sparing effect stems from the reduced exchange of sodium for potassium.
Pharmacokinetics:
- Absorption: Orally administered amiloride is absorbed moderately (around 50%). Food can enhance absorption.
- Metabolism: Amiloride is not metabolized by the liver and is excreted unchanged.
- Elimination: Primarily eliminated by the kidneys (around 50% in urine) with some fecal excretion (about 40%). Half-life is 6-9 hours in individuals with normal renal function.
Mode of Action: Amiloride directly blocks ENaCs, inhibiting passive sodium influx into renal epithelial cells. This action is independent of aldosterone.
Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Direct ENaC blocker. No significant interaction with other receptors, enzymes, or neurotransmitters.
Elimination Pathways: Renal excretion (approximately 50%) and fecal excretion (approximately 40%).
Dosage
Standard Dosage
Adults:
- Hypertension/Edema: 5 mg orally once daily, may be increased to 10 mg/day if needed. Maximum: 20 mg/day, although higher doses (up to 40 mg/day) have been used.
- With Thiazide Diuretics: 5 mg/day, adjusted as needed.
Children:
- Off-label use; safety and efficacy not fully established.
- Hypertension (Off-label): 0.625 mg/kg/day; not to exceed 20 mg/day. Nephrogenic diabetes insipidus (with hydrochlorothiazide): 0.3 mg/kg/day in divided doses.
Special Cases:
- Elderly Patients: Start with lower doses (e.g., 5 mg every other day) and titrate cautiously, monitoring renal function and potassium levels.
- Patients with Renal Impairment: Reduce dose by 50% for creatinine clearance (CrCl) 25-80 mL/min. Not recommended for CrCl < 25 mL/min.
- Patients with Hepatic Dysfunction: No specific dose adjustment is recommended but use with caution and monitor for electrolyte imbalances and signs of hepatic encephalopathy.
- Patients with Comorbid Conditions: Careful monitoring for hyperkalemia, particularly in patients with diabetes or heart disease.
Clinical Use Cases
Amiloride is not typically used in the following clinical settings:
- Intubation
- Surgical Procedures
- Mechanical Ventilation
- Intensive Care Unit (ICU) Use
- Emergency Situations
Dosage Adjustments
Adjust based on renal function, concomitant medications (especially ACE inhibitors, ARBs, potassium supplements), and electrolyte levels.
Side Effects
Common Side Effects
- Nausea, vomiting, anorexia, abdominal pain, flatulence, diarrhea, constipation
- Headache, dizziness, weakness, fatigue
- Skin rash
Rare but Serious Side Effects
- Hyperkalemia (high potassium levels)
- Electrolyte imbalances
- Hepatic encephalopathy (in patients with pre-existing liver disease)
Long-Term Effects
Chronic hyperkalemia can lead to cardiac arrhythmias and other complications.
Adverse Drug Reactions (ADR)
Hyperkalemia, potentially fatal if not treated promptly.
Contraindications
- Hyperkalemia
- Concurrent use of potassium-sparing diuretics or potassium supplements
- Severe renal impairment (anuria, acute/chronic renal failure)
- Hypersensitivity to amiloride
Drug Interactions
- ACE inhibitors, ARBs: Increased risk of hyperkalemia.
- Lithium: Reduced renal clearance of lithium, increasing risk of toxicity.
- NSAIDs: May reduce diuretic and antihypertensive effects.
- Cyclosporine, Tacrolimus: Increased risk of hyperkalemia.
- Other potassium-sparing diuretics: Additive potassium-sparing effects, high risk of hyperkalemia.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: B (Animal studies have not shown fetal harm, but there are no adequate and well-controlled studies in pregnant women).
- Breastfeeding: Amiloride may be excreted in breast milk. Use with caution and monitor the infant.
Drug Profile Summary
- Mechanism of Action: Blocks ENaCs, reducing sodium reabsorption and potassium loss.
- Side Effects: Nausea, vomiting, headache, hyperkalemia (serious).
- Contraindications: Hyperkalemia, severe renal impairment, concurrent use of potassium-sparing agents.
- Drug Interactions: ACE inhibitors, ARBs, lithium, NSAIDs.
- Pregnancy & Breastfeeding: Category B; use with caution during breastfeeding.
- Dosage: 5-10 mg/day; adjust based on renal function and other factors.
- Monitoring Parameters: Serum potassium, other electrolytes, renal function.
Popular Combinations
- Hydrochlorothiazide (Moduretic): Combines the potassium-sparing effects of amiloride with the enhanced diuresis of hydrochlorothiazide.
Precautions
- General Precautions: Monitor serum potassium closely.
- Specific Populations: Use with caution in elderly patients and those with renal or hepatic impairment.
- Lifestyle Considerations: No specific restrictions on alcohol, smoking, or diet, but address these as part of overall hypertension management.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Amiloride?
A: The initial dose is typically 5 mg/day, with a maximum of 20 mg/day for hypertension and edema. The dose may be adjusted based on the patient’s response and renal function.
Q2: What are the primary side effects of Amiloride?
A: Common side effects include nausea, vomiting, headache, dizziness, and skin rash. The most serious side effect is hyperkalemia (elevated potassium).
Q3: How does Amiloride differ from other diuretics?
A: Unlike thiazide and loop diuretics, amiloride conserves potassium, making it suitable for patients at risk of hypokalemia.
Q4: What are the contraindications to using Amiloride?
A: Amiloride is contraindicated in patients with hyperkalemia, severe renal impairment, or hypersensitivity to the drug. Concurrent use of other potassium-sparing diuretics or potassium supplements is also contraindicated.
Q5: How should Amiloride be used in patients with renal impairment?
A: The dose should be reduced in patients with moderate renal impairment. Amiloride is not recommended in patients with severe renal dysfunction.
Q6: Can Amiloride be used during pregnancy?
A: Amiloride is classified as Pregnancy Category B, meaning that animal studies haven’t revealed fetal harm. However, its use during pregnancy should be carefully considered and limited to situations where the potential benefits clearly outweigh the risks. Consult with an obstetrician.
Q7: Does Amiloride interact with other medications?
A: Yes, amiloride can interact with ACE inhibitors, ARBs, lithium, NSAIDs, and other medications. It’s important to review a patient’s medication list for potential interactions.
Q8: What should be monitored in patients taking Amiloride?
A: Serum potassium and other electrolytes, as well as renal function, should be closely monitored, especially during initial treatment and dose adjustments.
Q9: Can Amiloride be used in children?
A: Amiloride is not routinely used in children, but off-label use is possible in certain conditions. Pediatric dosing requires careful consideration based on weight and the specific condition being treated. Monitor closely.
