Usage
- Amiloride + Hydrochlorothiazide is prescribed for the treatment of hypertension (high blood pressure) and edema (fluid retention) associated with congestive heart failure. It is particularly useful in patients prone to hypokalemia (low potassium levels) induced by thiazide diuretics.
- Pharmacological classification: Potassium-sparing diuretic combined with a thiazide diuretic.
- Mechanism of action: This combination increases urination by promoting the excretion of sodium and water by the kidneys, while simultaneously conserving potassium. Hydrochlorothiazide inhibits sodium reabsorption in the distal convoluted tubule, while amiloride blocks sodium channels in the collecting duct, preventing potassium loss. This synergistic action addresses both fluid retention and electrolyte imbalance.
Alternate Names
- Generic Name: Amiloride hydrochloride/Hydrochlorothiazide
- Brand Name: Moduretic (no longer available as a brand name, only generic formulations are currently marketed)
How It Works
- Pharmacodynamics: The combination reduces blood volume through diuresis, leading to lower blood pressure. Amiloride’s potassium-sparing effect mitigates hydrochlorothiazide’s tendency to cause hypokalemia.
- Pharmacokinetics: Both drugs are orally administered and well-absorbed. Amiloride is primarily excreted unchanged in the urine, while hydrochlorothiazide undergoes some hepatic metabolism before renal excretion.
- Mode of Action: Hydrochlorothiazide inhibits the sodium-chloride symporter in the distal convoluted tubule of the nephron, reducing sodium reabsorption. Amiloride blocks epithelial sodium channels in the collecting duct, preventing sodium reabsorption and potassium secretion.
- Elimination pathways: Primarily renal excretion for both drugs.
Dosage
Standard Dosage
Adults:
- Initial dose: One tablet containing 5 mg amiloride and 50 mg hydrochlorothiazide once daily, taken with food.
- Maximum dose: Two tablets (10 mg amiloride/100 mg hydrochlorothiazide) per day, typically given as a single dose but may be divided.
Children:
- Not recommended for children under 18 years of age. Safety and efficacy have not been established in this population.
Special Cases:
- Elderly Patients: Start at the lower end of the dosing range (5mg/50mg) due to potential age-related decreases in renal function.
- Patients with Renal Impairment: Contraindicated in severe renal impairment (anuria, acute or chronic renal failure), including diabetic nephropathy. Use with caution in mild to moderate impairment, with close monitoring of serum electrolytes and renal function.
- Patients with Hepatic Dysfunction: Use with caution. Dosage adjustments may not be necessary, but close monitoring is recommended.
- Patients with Comorbid Conditions: Use with caution in patients with diabetes, gout, systemic lupus erythematosus, and other conditions affecting electrolyte balance or renal function.
Clinical Use Cases
This medication’s primary indications are hypertension and heart failure-related edema. Specific dosing for scenarios like intubation, surgery, mechanical ventilation, or ICU use is not generally indicated, as the dosage is based on the underlying condition being treated.
Dosage Adjustments
- Dose adjustments may be required in patients with renal or hepatic impairment, as described above. Patients with other comorbid conditions may also require careful monitoring and dosage adjustments.
Side Effects
Common Side Effects
- Headache
- Dizziness
- Nausea
- Vomiting
- Loss of appetite
- Diarrhea
- Constipation
- Fatigue
Rare but Serious Side Effects
- Severe allergic reactions (e.g., hives, difficulty breathing, swelling of the face, lips, tongue, or throat)
- Hyperkalemia (high potassium levels)
- Hyponatremia (low sodium levels)
- Dehydration
- Hypotension (low blood pressure)
- Gout
- Pancreatitis
- Liver damage
- Visual disturbances (blurred vision, yellowing of the eyes)
- Skin reactions
Long-Term Effects
- Electrolyte imbalances
- Impaired glucose tolerance
- Increased cholesterol and triglyceride levels
- Increased risk of non-melanoma skin cancer with prolonged hydrochlorothiazide use
Contraindications
- Hyperkalemia
- Severe renal impairment (anuria, acute or chronic renal failure), including diabetic nephropathy
- Concomitant use of potassium-sparing diuretics or potassium supplements
- Hypersensitivity to amiloride, hydrochlorothiazide, or sulfonamides
Drug Interactions
- Potassium supplements and potassium-sparing diuretics (increased risk of hyperkalemia)
- Lithium (increased lithium levels)
- Digoxin (increased digoxin toxicity in the presence of hypokalemia)
- Antidiabetic medications (altered glucose control)
- Nonsteroidal anti-inflammatory drugs (NSAIDs) (decreased diuretic effect)
- Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) (increased risk of hypotension and hyperkalemia)
- Alcohol (additive hypotensive effects)
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Not established. Use only if clearly needed, and weigh the potential benefits against the risks to the fetus.
- Breastfeeding: Hydrochlorothiazide is excreted in breast milk. Amiloride’s excretion is unknown but potential for adverse effects in infants exists. It is generally recommended to discontinue breastfeeding or the drug.
Drug Profile Summary
- Mechanism of Action: Combined potassium-sparing and thiazide diuretic, increasing urine output while conserving potassium.
- Side Effects: Common: headache, dizziness, nausea, vomiting, loss of appetite, diarrhea, constipation. Serious: hyperkalemia, hyponatremia, dehydration, hypotension.
- Contraindications: Hyperkalemia, severe renal impairment, concomitant potassium-sparing diuretics/supplements, hypersensitivity.
- Drug Interactions: Potassium supplements, lithium, digoxin, antidiabetics, NSAIDs, ACE inhibitors, ARBs.
- Pregnancy & Breastfeeding: Not recommended unless clearly needed.
- Dosage: Adults: 5/50 mg once daily, up to 10/100 mg. Children: Not recommended.
- Monitoring Parameters: Serum electrolytes (potassium, sodium, chloride), renal function (BUN, creatinine), blood glucose, uric acid.
Popular Combinations
- Not commonly combined with other drugs. It is itself a combination product designed to achieve the desired therapeutic effect while minimizing potassium loss.
Precautions
- General Precautions: Assess renal function, electrolyte levels, and blood glucose before and during treatment.
- Specific Populations: See “Special Cases” under Dosage.
- Lifestyle Considerations: Patients should be advised to avoid excessive alcohol intake and prolonged sun exposure. Driving may be impaired due to dizziness or hypotension.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Amiloride + Hydrochlorothiazide?
A: The initial dose for adults is 5/50 mg once daily with food. This may be increased to a maximum of 10/100 mg per day if necessary. It’s not recommended for children.
Q2: What are the most common side effects?
A: Headache, dizziness, nausea, vomiting, loss of appetite, diarrhea, and constipation are common side effects.
Q3: When is Amiloride + Hydrochlorothiazide contraindicated?
A: It’s contraindicated in patients with hyperkalemia, severe renal impairment, concurrent use of potassium-sparing diuretics or supplements, and hypersensitivity to its components.
Q4: How does this medication interact with other drugs?
A: Clinically significant interactions can occur with potassium supplements, lithium, digoxin, antidiabetic drugs, NSAIDs, ACE inhibitors, and ARBs. Always review a patient’s medication list for potential interactions.
Q5: Can this drug be used during pregnancy or breastfeeding?
A: It’s generally avoided during pregnancy and breastfeeding unless the benefits outweigh the potential risks. Consult with a specialist regarding potential risks and alternative therapies.
Q6: How should I monitor patients on Amiloride + Hydrochlorothiazide?
A: Monitor serum electrolytes (potassium, sodium, chloride), renal function (BUN, creatinine), blood glucose levels, and uric acid levels.
Q7: What should patients be advised regarding lifestyle modifications?
A: Advise patients to limit alcohol intake, avoid prolonged sun exposure, and be cautious about driving or operating machinery due to potential dizziness or hypotension.
Q8: What is the difference between amiloride/hydrochlorothiazide and using amiloride or hydrochlorothiazide alone?
A: Amiloride + Hydrochlorothiazide combines the actions of two different types of diuretics. Amiloride is a potassium-sparing diuretic that helps prevent the loss of potassium, while hydrochlorothiazide is a thiazide diuretic that helps to remove excess fluid from the body. Taking them together provides a more comprehensive approach to managing certain medical conditions and reducing side effects associated with taking either medication alone.
Q9: Does food affect how well amiloride + hydrochlorothiazide works?
A: Yes. It is recommended that you take amiloride + hydrochlorothiazide with food. Food helps to improve the absorption of the medication into the bloodstream, making it more effective at managing your medical condition.
