- ACRONYMS AND DEFINITIONS
- ENaC - Epithelial sodium channel
- HCTZ - Hydrochlorothiazide
- ENaC INHIBITORS
Amiloride (Midamor®)
Dosage forms
Tablet
- 5 mg
Dosing
Prevention / treatment of hypokalemia with other diuretics
- Starting: 5 mg once daily
- Maintenance: 5 - 10 mg once daily
- Max: 20 mg/day
- Doses > 10 mg a day have not been studied extensively
- Take with food
Generic / Price
- YES/$Other
- Typically prescribed with thiazide or loop diuretics for its potassium-conserving effects
- Amiloride has insignificant diuretic and antihypertensive effects
Triamterene (Dyrenium®)
Dosage forms
Capsule
- 50 mg
- 100 mg
Dosing
Prevention / treatment of hypokalemia with other diuretics
- Dosing: 37.5 - 75 mg a day
- May take without regard to food. Food may decrease stomach upset with monotherapy.
Edema (monotherapy)
- Starting: 100 mg twice a day after meals
- Max: 300 mg/day
- May take without regard to food. Food may decrease stomach upset with monotherapy.
Generic / Price
- YES/$$-$$$Other
- Typically prescribed with thiazide or loop diuretics for its potassium-conserving effects
- May promote increased diuresis when patients prove resistant or only partially responsive to thiazides or other diuretics because of secondary hyperaldosteronism
- THIAZIDE + ENaC INHIBITOR
Dyazide® (HCTZ + triamterene)
Dosage forms
Capsule
- HCTZ - Triamterene
- 25 mg - 37.5 mg
Dosing
Hypertension or Edema
- Dosing: 25/37.5 - 50/75 mg once daily
- Max: 50/75 mg once daily
- May take without regard to food
Generic / Price
- YES/$Other
- Triamterene helps prevent potassium loss from HCTZ but has no significant effect on blood pressure
Maxzide® (HCTZ + triamterene)
Dosage forms
Tablet
- HCTZ - Triamterene
- 25 mg - 37.5 mg
- 50 mg - 75 mg
Dosing
Hypertension or Edema
- Dosing: 25/37.5 - 50/75 mg once daily
- Max: 50/75 mg once daily
- May take without regard to food
Generic / Price
- YES/$Other
- Triamterene helps prevent potassium loss from HCTZ but has no significant effect on blood pressure
Moduretic® (HCTZ + amiloride)
Dosage forms
Tablet
- Amiloride - HCTZ
- 5 mg - 50 mg
Dosing
Hypertension or Edema
- Dosing: 5/50 mg - 10/100 mg/day
- May be given once daily or in divided doses
- Take with food
Generic / Price
- YES/$Other
- Amiloride helps prevent potassium loss from HCTZ but has no significant effect on blood pressure
- Kidney disease dosing
- ENaC inhibitors can raise potassium levels and should be used with caution in patients with kidney disease
- See elevated potassium
- If used in patients with suspected kidney disease, frequent lab monitoring of potassium is recommended
- The manufacturer's package insert for both drugs lists significant kidney disease as a contraindication to use
- Liver disease dosing
- Amiloride
- Amiloride is not metabolized by the liver
- Liver disease would not be expected to affect its clearance
- Triamterene
- Triamterene is contraindicated in patients with severe liver disease
- DRUG INTERACTIONS
- NOTE: Drug interactions presented here are NOT all-inclusive. Other interactions may exist. The interactions presented here are meant to encompass commonly prescribed medications and/or interactions that are well-documented. Always consult your physician or pharmacist before taking medications concurrently. CLICK HERE for more information on drug interactions.
- Amiloride and triamterene
- Lithium - ENaC inhibitors may reduce the clearance of lithium. ENaC inhibitors should not be taken with lithium if possible. Lithium levels should be monitored closely in patients taking ENaC inhibitors..
- Medications that can raise potassium levels - ENaC inhibitors have the potential to raise potassium levels and cause hyperkalemia. When combined with other potassium-raising medications, the risk is increased. While it may be appropriate to prescribe ENaC inhibitors with these medications, patients and providers should be aware of the potential risks. See RAAS inhibitor-induced hyperkalemia for recommendations on addressing hyperkalemia induced by these medications.
- Examples of medications that may raise potassium levels include:
- Aldosterone antagonists (spironolactone and eplerenone)
- ARBs (valsartan, olmesartan, etc.)
- ACE inhibitors
- Aliskiren (Tekturna®)
- Cyclosporine (Neoral®)
- Finerenone (Kerendia®)
- Heparin - heparin raises potassium secondarily by inhibiting aldosterone synthesis. LMWH does not appear to have the same effect. [1]
- Penicillin G potassium injection (1 million units contains 1.68mEq of potassium)
- Potassium supplements (K-Dur®, etc)
- Tacrolimus (Prograf®)
- Trimethoprim (part of Bactrim® and Septra®)
- Voclosporin (Lupkynis®)
- NSAIDS (Advil®, ibuprofen, naprosyn, etc.) - NSAIDS can block the therapeutic effect of ENaC inhibitors. Patients should monitor for decreased effectiveness of ENaC inhibitors when taking NSAIDS for extended periods.
- Salt substitutes (No-Salt®, etc.) - Salt substitutes typically contain a high amount of potassium (16.4 mEq per 1/4 teaspoon). Since ENaC inhibitors can raise potassium levels, caution should be used when consuming salt substitutes.
- Triamterene
- Nondepolarizing skeletal muscle relaxants - triamterene may potentiate the effect of muscle relaxants used during anesthesia
- Metabolism and clearance
- PRICE ($) INFO
Pricing legend
- $ = 0 - $50
- $$ = $51 - $100
- $$$ = $101 - $150
- $$$$ = > $150
- Pricing based on one month of therapy at standard dosing in an adult
- Pricing based on information from GoodRX.com®
- Pricing may vary by region and availability
- BIBLIOGRAPHY
- Manufacturer's package insert
- 1 - PMID 22560830 - Use and safety of unfractionated heparin for anticoagulation during maintenance hemodialysis, Am J Kidney Dis (2012)