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    Other Potassium-Sparing Diuretics

    DEA CLASS

    Rx

    DESCRIPTION

    Oral potassium-sparing diuretic similar in action to triamterene; not a thiazide; used in the treatment or prevention of hypokalemia; also for edema and as an adjunct in HTN; has little antihypertensive or diuretic activity compared with other diuretics, some additive effects noted when used concurrently with thiazides or loop diuretics; useful for those not tolerating or not unresponsive to potassium supplements.

    COMMON BRAND NAMES

    Midamor

    HOW SUPPLIED

    Amiloride/Amiloride Hydrochloride/Midamor Oral Tab: 5mg

    DOSAGE & INDICATIONS

    For the adjunctive treatment of heart failure edema, hypertension, or hypokalemia.
    NOTE: Amiloride rarely should be used alone due to its weak diuretic and antihypertensive effects and its associated risk of hyperkalemia (10% when used as a single agent). Amiloride is indicated as adjunctive treatment with thiazide or loop diuretics to treat heart failure or hypertension, when it is clinically important to prevent hypokalemia or when persistent hypokalemia has been documented.
    Oral dosage
    Adults

    Initially, 5 to 10 mg/day PO. Titrate the dosage to achieve clinical goals. Carefully monitor serum potassium and electrolyte balance. Max: 20 mg/day. Heart failure guidelines recommend adding a diuretic to standard therapy for reduced ejection fraction heart failure (HFrEF) patients with volume overload. Diuretics should also be used in preserved ejection fraction heart failure (HFpEF).

    Children† and Adolescents†

    0.4 to 0.625 mg/kg/dose PO once daily. Max: 20 mg/day.

    For the treatment of ascites† (e.g., due to hepatic cirrhosis) alone or in combination with furosemide.
    Oral dosage
    Adults

    10 mg PO once daily. Maximum dose is 40 mg/day. Titrate the dosage to achieve clinical goals; carefully monitor serum potassium and electrolyte balance.

    Geriatric

    See adult dosage. Elderly patients may be more sensitive to the diuretic effects of the drug and are more likely to have age-associated renal dysfunction (see renal dosing).

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    20 mg/day PO (manufacturer guidelines); 40 mg/day PO has been used.

    Geriatric

    20 mg/day PO (manufacturer guidelines); 40 mg/day PO has been used.

    Adolescents

    Safety and efficacy have not been established; however, doses up to 0.625 mg/kg/day PO (Max: 20 mg/day) have been recommended.

    Children

    Safety and efficacy have not been established; however, doses up to 0.625 mg/kg/day PO (Max: 20 mg/day) have been recommended.

    Infants

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    No specific dosage adjustment is needed in patients with hepatic impairment; see dosage for the treatment of ascites. Amiloride is not metabolized by the liver; however, drug accumulation may occur in patients with hepatorenal syndrome (see renal dosing). In general, diuretics should be used with caution in patients with hepatic disease since minor alterations of fluid and electrolyte balance may precipitate hepatic coma.

    Renal Impairment

    CrCl > 50 mL/min: No dosage adjustment needed.
    CrCl 10—50 mL/min: Reduce the recommended dose by 50%; however, amiloride should generally be avoided due to the risk of hyperkalemia. If amiloride use is necessary, monitor serum potassium closely.
    CrCl < 10 mL/min: Contraindicated in patients with renal failure or anuria.
     
    Intermittent hemodialysis
    Amiloride is contraindicated in patients with renal failure or anuria.

    ADMINISTRATION

    Oral Administration

    Administer amiloride with food to minimize gastrointestinal effects.

    STORAGE

    Midamor:
    - Store at room temperature (between 59 to 86 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    Anuria, diabetes mellitus, diabetic nephropathy, hyperkalemia, renal disease, renal failure, renal impairment

    Amiloride is contraindicated in patients with hyperkalemia (serum potassium greater than 5.5 mEq/L) and in patients receiving other potassium-sparing agents because rapid increases in plasma potassium could occur. Patients receiving amiloride should not receive potassium supplementation or increase their dietary intake of potassium unless they have refractory hypokalemia; serum potassium, creatinine, and BUN levels should be monitored. Amiloride-induced hyperkalemia can cause life-threatening cardiac arrhythmias and is more likely to occur in patients with impaired renal function, diabetes mellitus, or in elderly patients. Amiloride should be used with caution in these patients. These patients should have periodic serum electrolyte, creatinine, and BUN levels monitored. The precaution for amiloride in patients with diabetes mellitus is primarily due to the risk of hyperkalemia and not the risk of inducing hyperglycemia, which may occur with thiazide or loop diuretics. Amiloride is also contraindicated in patients with anuria, diabetic nephropathy, or any renal disease associated with acute or chronic renal insufficiency (CrCl less than 10 mL/minute), severe renal impairment, or renal failure. Amiloride should generally be avoided in patients with mild to moderate renal impairment (CrCl 10 to 50 mL/minute) due to the risk of hyperkalemia. Patients with evidence of renal functional impairment (BUN greater than 30 mg/dL or Scr higher than 1.5 mg/dL) or diabetes mellitus should not receive the drug without careful, frequent and continuing monitoring of serum electrolytes, creatinine, and BUN levels. Potassium retention associated with potassium-sparing diuretic use is accentuated in the presence of renal impairment and may result in the rapid development of hyperkalemia. To avoid hyperkalemia, serum potassium, creatinine, and BUN levels should be monitored in all patients receiving amiloride.

    Hyponatremia

    Amiloride should be used with caution in patients with preexisting hyponatremia. Amiloride can cause hyponatremia and may worsen this condition.

    Hepatic disease

    Amiloride-induced fluctuations in serum electrolyte concentrations can occur rapidly and precipitate hepatic encephalopathy in susceptible patients. Therefore, amiloride should be used with caution in patients with hepatic disease.

    Acid/base imbalance, metabolic acidosis, respiratory acidosis

    Patients with significant acid/base imbalance should have their condition corrected before diuretics such as amiloride are initiated. Close monitoring of the acid-base status is required in debilitated patients or severely ill patients in whom respiratory acidosis or metabolic acidosis may occur (e.g., cardiopulmonary disease or uncontrolled diabetes). These patients are at a higher risk for developing sudden metabolic acidosis or respiratory acidosis, with resultant rapid increases in serum potassium concentrations that could be exacerbated by potassium-sparing diuretic therapy.

    Pregnancy

    Amiloride is classified as pregnancy category B. There are no adequate and well-controlled studies in pregnant women. According to the manufacturer, the drug should be administered to pregnant women only when the potential benefits to the mother outweigh the potential risk to the fetus. In general, diuretics are contraindicated in pregnant women with mild edema that is unresponsive to supportive measures (elevation of the lower extremities and the use of support hose) and edema which is not associated with more severe disease. Diuretics do not prevent the development of toxemia of pregnancy.

    Breast-feeding

    According to the manufacturer, a decision should be made whether to discontinue breast-feeding or to discontinue amiloride. It is not known whether amiloride is excreted in human milk ; however, the molecular weight of the drug is low enough for excretion into breast-milk to occur. Amiloride has not been evaluated by the American Academy of Pediatrics (AAP). Spironolactone is classified by the AAP as usually compatible with breast-feeding and may represent a reasonable alternative for some patients. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    Children

    While studies have not documented pediatric-specific problems, the safety and efficacy of amiloride have not been established in children.

    Geriatric

    Reported clinical experience with amiloride has not identified differences in responses between geriatric and younger adult patients. Dose selection for the geriatric patient should generally be cautious, usually starting at the low end of the dosing range. It may also be useful to monitor renal function. According to the Beers Criteria, diuretics are considered potentially inappropriate medications (PIMs) in geriatric patients; use with caution due to the potential for causing or exacerbating SIADH or hyponatremia; sodium levels should be closely monitored when starting or changing dosages of diuretics in older adults. The Beers expert panel recommends that amiloride be avoided in geriatric patients with a creatinine clearance less than 30 mL/minute due to the potential for increased potassium and decreased sodium. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities; antihypertensive regimens should be individualized to achieve the desired outcome while minimizing adverse effects. Antihypertensives may cause dizziness, postural hypotension, fatigue, and there is an increased risk for falls. Diuretics may cause fluid and electrolyte imbalances and may precipitate or exacerbate urinary incontinence.

    ADVERSE REACTIONS

    Severe

    hyperkalemia / Delayed / 10.0-10.0
    peptic ulcer / Delayed / 0-1.0
    GI bleeding / Delayed / 0-1.0
    aplastic anemia / Delayed / 0-1.0
    visual impairment / Early / 0-1.0

    Moderate

    constipation / Delayed / 1.0-3.0
    encephalopathy / Delayed / 1.0-3.0
    impotence (erectile dysfunction) / Delayed / 1.0-3.0
    dyspnea / Early / 1.0-3.0
    confusion / Early / 0-1.0
    chest pain (unspecified) / Early / 0-1.0
    depression / Delayed / 0-1.0
    neutropenia / Delayed / 0-1.0
    bladder spasm / Early / 0-1.0
    dysuria / Early / 0-1.0
    orthostatic hypotension / Delayed / 0-1.0
    angina / Early / 0-1.0
    palpitations / Early / 0-1.0
    jaundice / Delayed / 0-1.0
    elevated hepatic enzymes / Delayed / 0-1.0
    hyponatremia / Delayed / Incidence not known
    hypochloremia / Delayed / Incidence not known
    metabolic acidosis / Delayed / Incidence not known

    Mild

    anorexia / Delayed / 3.0-8.0
    nausea / Early / 3.0-8.0
    diarrhea / Early / 3.0-8.0
    vomiting / Early / 3.0-8.0
    headache / Early / 3.0-8.0
    abdominal pain / Early / 1.0-3.0
    dizziness / Early / 1.0-3.0
    weakness / Early / 1.0-3.0
    cough / Delayed / 1.0-3.0
    flatulence / Early / 0-1.0
    xerostomia / Early / 0-1.0
    dyspepsia / Early / 0-1.0
    myalgia / Early / 0-1.0
    anxiety / Delayed / 0-1.0
    tremor / Early / 0-1.0
    vertigo / Early / 0-1.0
    back pain / Delayed / 0-1.0
    arthralgia / Delayed / 0-1.0
    insomnia / Early / 0-1.0
    musculoskeletal pain / Early / 0-1.0
    drowsiness / Early / 0-1.0
    increased urinary frequency / Early / 0-1.0
    polyuria / Early / 0-1.0
    gynecomastia / Delayed / 0-1.0
    tinnitus / Delayed / 0-1.0
    nasal congestion / Early / 0-1.0
    pruritus / Rapid / 0-1.0
    alopecia / Delayed / 0-1.0
    rash / Early / 0-1.0

    DRUG INTERACTIONS

    Abacavir; Dolutegravir; Lamivudine: (Moderate) Drugs that are actively secreted via cationic tubular secretion, such as amiloride, should be co-administered with caution with lamivudine since they could increase lamivudine plasma concentrations, and therefore lamivudine associated adverse reactions, via potential competition for renal cationic secretion.
    Abacavir; Lamivudine, 3TC: (Moderate) Drugs that are actively secreted via cationic tubular secretion, such as amiloride, should be co-administered with caution with lamivudine since they could increase lamivudine plasma concentrations, and therefore lamivudine associated adverse reactions, via potential competition for renal cationic secretion.
    Abacavir; Lamivudine, 3TC; Zidovudine, ZDV: (Moderate) Drugs that are actively secreted via cationic tubular secretion, such as amiloride, should be co-administered with caution with lamivudine since they could increase lamivudine plasma concentrations, and therefore lamivudine associated adverse reactions, via potential competition for renal cationic secretion.
    Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Salicylates can increase the risk of renal insufficiency in patients receiving diuretics, secondary to effects on renal blood flow. Salicylates inhibit renal prostaglandin production, which causes salt and water retention and decreased renal blood flow. Coadministration may cause hyperkalemia.
    Acetaminophen; Butalbital; Caffeine; Codeine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when a potassium sparing diuretic is administered with codeine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
    Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Moderate) Salicylates can increase the risk of renal insufficiency in patients receiving diuretics, secondary to effects on renal blood flow. Salicylates inhibit renal prostaglandin production, which causes salt and water retention and decreased renal blood flow. Coadministration may cause hyperkalemia.
    Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Moderate) Salicylates can increase the risk of renal insufficiency in patients receiving diuretics, secondary to effects on renal blood flow. Salicylates inhibit renal prostaglandin production, which causes salt and water retention and decreased renal blood flow. Coadministration may cause hyperkalemia.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Acetaminophen; Codeine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when a potassium sparing diuretic is administered with codeine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
    Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Acetaminophen; Hydrocodone: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when amiloride is administered with hydrocodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
    Acetaminophen; Oxycodone: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when amiloride is administered with oxycodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
    Acetaminophen; Pentazocine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when potassium-sparring diuretics are administered with pentazocine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
    Acetaminophen; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Acetaminophen; Tramadol: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when potassium-sparing diuretics are administered with tramadol. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
    Acetazolamide: (Moderate) Carbonic anhydrase inhibitors promote electrolyte excretion including hydrogen ions, sodium, and potassium. They can enhance the sodium depleting effects of other diuretics when used concurrently. Pre-existing hypokalemia and hyperuricemia can also be potentiated by carbonic anhydrase inhibitors. Monitor serum potassium to determine the need for potassium supplementation and alteration in drug therapy.
    Acrivastine; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Adefovir: (Moderate) Adefovir is eliminated renally by a combination of glomerular filtration and active tubular secretion. Coadministration of adefovir dipivoxil with drugs that reduce renal function or compete for active tubular secretion, such as amiloride, may decrease adefovir elimination by competing for common renal tubular transport systems, thereby increasing serum concentrations of adefovir and/or amiloride. Coadministration of these drugs has not been studied, but caution is warranted.
    Aldesleukin, IL-2: (Moderate) Potassium sparing diuretics may potentiate the hypotension seen with aldesleukin, IL 2.
    Alemtuzumab: (Moderate) Alemtuzumab may cause hypotension. Careful monitoring of blood pressure and hypotensive symptoms is recommended especially in patients with ischemic heart disease and in patients on antihypertensive agents.
    Alfentanil: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when a potassium sparing diuretic is administered with alfentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
    Aliskiren: (Moderate) Due to the risk of hyperkalemia, drugs that increase serum potassium concentration, such as potassium-sparing diuretics, should be used cautiously in patients taking aliskiren. Electrolytes should be routinely monitored in patients receiving aliskiren. Aliskiren can enhance the effects of diuretics on blood pressure if given concomitantly. This additive effect may be desirable, but dosages must be adjusted accordingly. Also, patients with hyponatremia or hypovolemia may become hypotensive and/or develop reversible renal insufficiency when given aliskiren and diuretics.
    Aliskiren; Amlodipine: (Moderate) Due to the risk of hyperkalemia, drugs that increase serum potassium concentration, such as potassium-sparing diuretics, should be used cautiously in patients taking aliskiren. Electrolytes should be routinely monitored in patients receiving aliskiren. Aliskiren can enhance the effects of diuretics on blood pressure if given concomitantly. This additive effect may be desirable, but dosages must be adjusted accordingly. Also, patients with hyponatremia or hypovolemia may become hypotensive and/or develop reversible renal insufficiency when given aliskiren and diuretics.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Due to the risk of hyperkalemia, drugs that increase serum potassium concentration, such as potassium-sparing diuretics, should be used cautiously in patients taking aliskiren. Electrolytes should be routinely monitored in patients receiving aliskiren. Aliskiren can enhance the effects of diuretics on blood pressure if given concomitantly. This additive effect may be desirable, but dosages must be adjusted accordingly. Also, patients with hyponatremia or hypovolemia may become hypotensive and/or develop reversible renal insufficiency when given aliskiren and diuretics.
    Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Due to the risk of hyperkalemia, drugs that increase serum potassium concentration, such as potassium-sparing diuretics, should be used cautiously in patients taking aliskiren. Electrolytes should be routinely monitored in patients receiving aliskiren. Aliskiren can enhance the effects of diuretics on blood pressure if given concomitantly. This additive effect may be desirable, but dosages must be adjusted accordingly. Also, patients with hyponatremia or hypovolemia may become hypotensive and/or develop reversible renal insufficiency when given aliskiren and diuretics.
    Aliskiren; Valsartan: (Major) Potassium-sparing diuretics, such as amiloride, should be used with caution in patients taking drugs that may increase serum potassium levels such as angiotensin II receptor antagonists. Concurrent use can cause hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients. (Moderate) Due to the risk of hyperkalemia, drugs that increase serum potassium concentration, such as potassium-sparing diuretics, should be used cautiously in patients taking aliskiren. Electrolytes should be routinely monitored in patients receiving aliskiren. Aliskiren can enhance the effects of diuretics on blood pressure if given concomitantly. This additive effect may be desirable, but dosages must be adjusted accordingly. Also, patients with hyponatremia or hypovolemia may become hypotensive and/or develop reversible renal insufficiency when given aliskiren and diuretics.
    Alprostadil: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as spironolactone or other potassium-sparing diuretics, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
    Aluminum Hydroxide; Magnesium Hydroxide: (Moderate) Long-term use of potassium-sparing diuretics has been found to increase renal tubular reabsorption of magnesium which may cause hypermagnesemia in patients also receiving magnesium supplements, especially in patients with renal insufficiency.
    Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Moderate) Long-term use of potassium-sparing diuretics has been found to increase renal tubular reabsorption of magnesium which may cause hypermagnesemia in patients also receiving magnesium supplements, especially in patients with renal insufficiency.
    Ambrisentan: (Moderate) Although no specific interactions have been documented, ambrisentan has vasodilatory effects and may contribute additive hypotensive effects when given with other antihypertensive agents. Patients receiving ambrisentan in combination with other antihypertensive agents should be monitored for decreases in blood pressure.
    Amifostine: (Major) Patients receiving antihypertensive agents should be closely monitored during amifostine infusions due to additive effects. If possible, patients should not take their antihypertensive medication 24 hours before receiving amifostine. Patients who can not stop their antihypertensive agents should not receive amifostine or be closely monitored during the infusion and, possibly, given lower doses.
    Aminosalicylate sodium, Aminosalicylic acid: (Moderate) Salicylates can increase the risk of renal insufficiency in patients receiving diuretics, secondary to effects on renal blood flow. Salicylates inhibit renal prostaglandin production, which causes salt and water retention and decreased renal blood flow. Coadministration may cause hyperkalemia.
    Amlodipine; Benazepril: (Major) Amiloride should be used very cautiously with agents that have potential to induce hyperkalemia; serum potassium levels monitored when such agents are coadministered with amiloride. Simultaneous use of a potassium-sparing diuretic (e.g., amiloride) with angiotensin-converting enzyme inhibitors (ACE inhibitors) can increase the risk of hyperkalemia, especially in the presence of renal impairment (renal disease, elderly patients). These agents should be used with caution and serum potassium levels monitored when the substances are coadministered. The Beers Criteria recommends avoiding routine use of this combination in older adults; reserve this combination for patients with demonstrated hypokalemia while taking an ACE inhibitor.
    Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan: (Major) Potassium-sparing diuretics, such as amiloride, should be used with caution in patients taking drugs that may increase serum potassium levels such as angiotensin II receptor antagonists. Concurrent use can cause hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
    Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: (Major) Potassium-sparing diuretics, such as amiloride, should be used with caution in patients taking drugs that may increase serum potassium levels such as angiotensin II receptor antagonists. Concurrent use can cause hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
    Amlodipine; Olmesartan: (Major) Potassium-sparing diuretics, such as amiloride, should be used with caution in patients taking drugs that may increase serum potassium levels such as angiotensin II receptor antagonists. Concurrent use can cause hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
    Amlodipine; Telmisartan: (Major) Potassium-sparing diuretics, such as amiloride, should be used with caution in patients taking drugs that may increase serum potassium levels such as angiotensin II receptor antagonists. Concurrent use can cause hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
    Amlodipine; Valsartan: (Major) Potassium-sparing diuretics, such as amiloride, should be used with caution in patients taking drugs that may increase serum potassium levels such as angiotensin II receptor antagonists. Concurrent use can cause hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
    Amobarbital: (Moderate) Concurrent use of amobarbital with antihypertensive agents may lead to hypotension. Monitor for decreases in blood pressure during times of coadministration.
    Amoxicillin: (Major) The administration of amiloride 2 hours before a dose of amoxicillin oral suspension reduced the bioavailability of amoxicillin by 27% and its Cmax by 25%. No change in the renal clearance of amoxicillin was noted. Although the significance of this pharmacokinetic interaction is unclear, clinicians should avoid administering doses of these two drugs within 2 hours of the other. Staggering the administration times further may avoid this interaction.
    Amoxicillin; Clarithromycin; Lansoprazole: (Major) The administration of amiloride 2 hours before a dose of amoxicillin oral suspension reduced the bioavailability of amoxicillin by 27% and its Cmax by 25%. No change in the renal clearance of amoxicillin was noted. Although the significance of this pharmacokinetic interaction is unclear, clinicians should avoid administering doses of these two drugs within 2 hours of the other. Staggering the administration times further may avoid this interaction.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) The administration of amiloride 2 hours before a dose of amoxicillin oral suspension reduced the bioavailability of amoxicillin by 27% and its Cmax by 25%. No change in the renal clearance of amoxicillin was noted. Although the significance of this pharmacokinetic interaction is unclear, clinicians should avoid administering doses of these two drugs within 2 hours of the other. Staggering the administration times further may avoid this interaction.
    Amoxicillin; Clavulanic Acid: (Major) The administration of amiloride 2 hours before a dose of amoxicillin oral suspension reduced the bioavailability of amoxicillin by 27% and its Cmax by 25%. No change in the renal clearance of amoxicillin was noted. Although the significance of this pharmacokinetic interaction is unclear, clinicians should avoid administering doses of these two drugs within 2 hours of the other. Staggering the administration times further may avoid this interaction.
    Amphetamine: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like potassium-sparing diuretics. Close monitoring of blood pressure is advised.
    Amphetamine; Dextroamphetamine Salts: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like potassium-sparing diuretics. Close monitoring of blood pressure is advised.
    Amphetamine; Dextroamphetamine: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like potassium-sparing diuretics. Close monitoring of blood pressure is advised.
    Amyl Nitrite: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
    Angiotensin II receptor antagonists: (Major) Potassium-sparing diuretics, such as amiloride, should be used with caution in patients taking drugs that may increase serum potassium levels such as angiotensin II receptor antagonists. Concurrent use can cause hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
    Angiotensin-converting enzyme inhibitors: (Major) Amiloride should be used very cautiously with agents that have potential to induce hyperkalemia; serum potassium levels monitored when such agents are coadministered with amiloride. Simultaneous use of a potassium-sparing diuretic (e.g., amiloride) with angiotensin-converting enzyme inhibitors (ACE inhibitors) can increase the risk of hyperkalemia, especially in the presence of renal impairment (renal disease, elderly patients). These agents should be used with caution and serum potassium levels monitored when the substances are coadministered. The Beers Criteria recommends avoiding routine use of this combination in older adults; reserve this combination for patients with demonstrated hypokalemia while taking an ACE inhibitor.
    Apomorphine: (Moderate) Use of potassium-sparing diuretics and apomorphine together can increase the hypotensive effects of apomorphine. Monitor blood pressure regularly during use of this combination.
    Apraclonidine: (Minor) Alpha blockers as a class may reduce heart rate and blood pressure. While no specific drug interactions have been identified with systemic agents and apraclonidine during clinical trials, it is theoretically possible that additive blood pressure reductions could occur when apraclonidine is combined with the use of antihypertensive agents. Patients using cardiovascular drugs concomitantly with apraclonidine should have their pulse and blood pressure monitored periodically.
    Aripiprazole: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Arsenic Trioxide: (Moderate) Use caution when using arsenic trioxide with potassium-sparing diuretics. Electrolyte abnormalities, such as increased potassium, may increase the risk for QT prolongation and torsade de pointes.
    Asenapine: (Moderate) Secondary to alpha-blockade, asenapine can produce vasodilation that may result in additive effects during concurrent use of antihypertensive agents. The potential reduction in blood pressure can precipitate orthostatic hypotension and associated dizziness, tachycardia, and syncope. If concurrent use of asenapine and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known.
    Aspirin, ASA: (Moderate) Salicylates can increase the risk of renal insufficiency in patients receiving diuretics, secondary to effects on renal blood flow. Salicylates inhibit renal prostaglandin production, which causes salt and water retention and decreased renal blood flow. Coadministration may cause hyperkalemia.
    Aspirin, ASA; Butalbital; Caffeine: (Moderate) Salicylates can increase the risk of renal insufficiency in patients receiving diuretics, secondary to effects on renal blood flow. Salicylates inhibit renal prostaglandin production, which causes salt and water retention and decreased renal blood flow. Coadministration may cause hyperkalemia.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when a potassium sparing diuretic is administered with codeine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. (Moderate) Salicylates can increase the risk of renal insufficiency in patients receiving diuretics, secondary to effects on renal blood flow. Salicylates inhibit renal prostaglandin production, which causes salt and water retention and decreased renal blood flow. Coadministration may cause hyperkalemia.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Salicylates can increase the risk of renal insufficiency in patients receiving diuretics, secondary to effects on renal blood flow. Salicylates inhibit renal prostaglandin production, which causes salt and water retention and decreased renal blood flow. Coadministration may cause hyperkalemia.
    Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Salicylates can increase the risk of renal insufficiency in patients receiving diuretics, secondary to effects on renal blood flow. Salicylates inhibit renal prostaglandin production, which causes salt and water retention and decreased renal blood flow. Coadministration may cause hyperkalemia.
    Aspirin, ASA; Carisoprodol: (Moderate) Salicylates can increase the risk of renal insufficiency in patients receiving diuretics, secondary to effects on renal blood flow. Salicylates inhibit renal prostaglandin production, which causes salt and water retention and decreased renal blood flow. Coadministration may cause hyperkalemia.
    Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when a potassium sparing diuretic is administered with codeine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. (Moderate) Salicylates can increase the risk of renal insufficiency in patients receiving diuretics, secondary to effects on renal blood flow. Salicylates inhibit renal prostaglandin production, which causes salt and water retention and decreased renal blood flow. Coadministration may cause hyperkalemia.
    Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Salicylates can increase the risk of renal insufficiency in patients receiving diuretics, secondary to effects on renal blood flow. Salicylates inhibit renal prostaglandin production, which causes salt and water retention and decreased renal blood flow. Coadministration may cause hyperkalemia.
    Aspirin, ASA; Dipyridamole: (Moderate) Salicylates can increase the risk of renal insufficiency in patients receiving diuretics, secondary to effects on renal blood flow. Salicylates inhibit renal prostaglandin production, which causes salt and water retention and decreased renal blood flow. Coadministration may cause hyperkalemia.
    Aspirin, ASA; Omeprazole: (Moderate) Salicylates can increase the risk of renal insufficiency in patients receiving diuretics, secondary to effects on renal blood flow. Salicylates inhibit renal prostaglandin production, which causes salt and water retention and decreased renal blood flow. Coadministration may cause hyperkalemia.
    Aspirin, ASA; Oxycodone: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when amiloride is administered with oxycodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. (Moderate) Salicylates can increase the risk of renal insufficiency in patients receiving diuretics, secondary to effects on renal blood flow. Salicylates inhibit renal prostaglandin production, which causes salt and water retention and decreased renal blood flow. Coadministration may cause hyperkalemia.
    Aspirin, ASA; Pravastatin: (Moderate) Salicylates can increase the risk of renal insufficiency in patients receiving diuretics, secondary to effects on renal blood flow. Salicylates inhibit renal prostaglandin production, which causes salt and water retention and decreased renal blood flow. Coadministration may cause hyperkalemia.
    Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Salicylates can increase the risk of renal insufficiency in patients receiving diuretics, secondary to effects on renal blood flow. Salicylates inhibit renal prostaglandin production, which causes salt and water retention and decreased renal blood flow. Coadministration may cause hyperkalemia.
    Azelastine; Fluticasone: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
    Azilsartan: (Major) Potassium-sparing diuretics, such as amiloride, should be used with caution in patients taking drugs that may increase serum potassium levels such as angiotensin II receptor antagonists. Concurrent use can cause hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
    Azilsartan; Chlorthalidone: (Major) Potassium-sparing diuretics, such as amiloride, should be used with caution in patients taking drugs that may increase serum potassium levels such as angiotensin II receptor antagonists. Concurrent use can cause hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
    Baclofen: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Beclomethasone: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
    Belladonna; Opium: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when amiloride is administered with opium. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
    Benazepril: (Major) Amiloride should be used very cautiously with agents that have potential to induce hyperkalemia; serum potassium levels monitored when such agents are coadministered with amiloride. Simultaneous use of a potassium-sparing diuretic (e.g., amiloride) with angiotensin-converting enzyme inhibitors (ACE inhibitors) can increase the risk of hyperkalemia, especially in the presence of renal impairment (renal disease, elderly patients). These agents should be used with caution and serum potassium levels monitored when the substances are coadministered. The Beers Criteria recommends avoiding routine use of this combination in older adults; reserve this combination for patients with demonstrated hypokalemia while taking an ACE inhibitor.
    Benazepril; Hydrochlorothiazide, HCTZ: (Major) Amiloride should be used very cautiously with agents that have potential to induce hyperkalemia; serum potassium levels monitored when such agents are coadministered with amiloride. Simultaneous use of a potassium-sparing diuretic (e.g., amiloride) with angiotensin-converting enzyme inhibitors (ACE inhibitors) can increase the risk of hyperkalemia, especially in the presence of renal impairment (renal disease, elderly patients). These agents should be used with caution and serum potassium levels monitored when the substances are coadministered. The Beers Criteria recommends avoiding routine use of this combination in older adults; reserve this combination for patients with demonstrated hypokalemia while taking an ACE inhibitor.
    Benzhydrocodone; Acetaminophen: (Moderate) Benzhydrocodone may reduce the efficacy of diuretics due to induction of the release of antidiuretic hormone. Adjustments to diuretic therapy may be needed in some patients. In addition, opiate agonists may potentiate orthostatic hypotension when used concurrently with diuretics.
    Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Salicylates can increase the risk of renal insufficiency in patients receiving diuretics, secondary to effects on renal blood flow. Salicylates inhibit renal prostaglandin production, which causes salt and water retention and decreased renal blood flow. Coadministration may cause hyperkalemia.
    Benzphetamine: (Minor) Benzphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like potassium-sparing diuretics. Close monitoring of blood pressure is advised.
    Betamethasone: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
    Bismuth Subsalicylate: (Moderate) Salicylates can increase the risk of renal insufficiency in patients receiving diuretics, secondary to effects on renal blood flow. Salicylates inhibit renal prostaglandin production, which causes salt and water retention and decreased renal blood flow. Coadministration may cause hyperkalemia.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Salicylates can increase the risk of renal insufficiency in patients receiving diuretics, secondary to effects on renal blood flow. Salicylates inhibit renal prostaglandin production, which causes salt and water retention and decreased renal blood flow. Coadministration may cause hyperkalemia.
    Bortezomib: (Moderate) Patients on antihypertensive agents receiving bortezomib treatment may require close monitoring of their blood pressure and dosage adjustment of their medication. During clinical trials of bortezomib, hypotension was reported in roughly 12 percent of patients.
    Bosentan: (Moderate) Although no specific interactions have been documented, bosentan has vasodilatory effects and may contribute additive hypotensive effects when given with diuretics.
    Brexpiprazole: (Moderate) Due to brexpiprazole's antagonism at alpha 1-adrenergic receptors, the drug may enhance the hypotensive effects of alpha-blockers and other antihypertensive agents.
    Brompheniramine; Carbetapentane; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Brompheniramine; Guaifenesin; Hydrocodone: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when amiloride is administered with hydrocodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when amiloride is administered with hydrocodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Brompheniramine; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Budesonide: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
    Budesonide; Formoterol: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
    Buprenorphine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when a potassium sparing diuretic is administered with buprenorphine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
    Buprenorphine; Naloxone: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when a potassium sparing diuretic is administered with buprenorphine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
    Cabergoline: (Minor) Cabergoline has minimal affinity for adrenergic receptors; however, it has been associated with hypotension in some instances. Cabergoline should be used cautiously in those receiving antihypertensive agents.
    Calcium Carbonate; Magnesium Hydroxide: (Moderate) Long-term use of potassium-sparing diuretics has been found to increase renal tubular reabsorption of magnesium which may cause hypermagnesemia in patients also receiving magnesium supplements, especially in patients with renal insufficiency.
    Calcium Phosphate, Supersaturated: (Moderate) Concomitant use of medicines with potential to alter renal perfusion or function such as diuretics may increase the risk of acute phosphate nephropathy in patients receiving sodium phosphate monobasic monohydrate; sodium phosphate dibasic anhydrous.
    Canagliflozin: (Major) When canagliflozin is initiated in patients already receiving diuretics, symptomatic hypotension can occur. Patients with impaired renal function (eGFR < 60 ml/min/1.73 m2), low systolic blood pressure, or who are elderly may also be at a greater risk. Before initiating canagliflozin in patients with one or more of these characteristics, volume status should be assessed and corrected. Monitor for signs and symptoms after initiating therapy. In addition, canagliflozin can lead to hyperkalemia. Patients treated with canagliflozin 300 mg/day were more likely to experience increases in potassium. Patients with moderate renal impairment who are taking medications that interfere with potassium excretion, such as potassium-sparing diuretics, are more likely to develop hyperkalemia. Monitor serum potassium levels periodically after initiating canagliflozin in patients with impaired renal function and in patients predisposed to hyperkalemia due to medications or other medical conditions.
    Canagliflozin; Metformin: (Major) When canagliflozin is initiated in patients already receiving diuretics, symptomatic hypotension can occur. Patients with impaired renal function (eGFR < 60 ml/min/1.73 m2), low systolic blood pressure, or who are elderly may also be at a greater risk. Before initiating canagliflozin in patients with one or more of these characteristics, volume status should be assessed and corrected. Monitor for signs and symptoms after initiating therapy. In addition, canagliflozin can lead to hyperkalemia. Patients treated with canagliflozin 300 mg/day were more likely to experience increases in potassium. Patients with moderate renal impairment who are taking medications that interfere with potassium excretion, such as potassium-sparing diuretics, are more likely to develop hyperkalemia. Monitor serum potassium levels periodically after initiating canagliflozin in patients with impaired renal function and in patients predisposed to hyperkalemia due to medications or other medical conditions.
    Candesartan: (Major) Potassium-sparing diuretics, such as amiloride, should be used with caution in patients taking drugs that may increase serum potassium levels such as angiotensin II receptor antagonists. Concurrent use can cause hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
    Candesartan; Hydrochlorothiazide, HCTZ: (Major) Potassium-sparing diuretics, such as amiloride, should be used with caution in patients taking drugs that may increase serum potassium levels such as angiotensin II receptor antagonists. Concurrent use can cause hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
    Captopril: (Major) Amiloride should be used very cautiously with agents that have potential to induce hyperkalemia; serum potassium levels monitored when such agents are coadministered with amiloride. Simultaneous use of a potassium-sparing diuretic (e.g., amiloride) with angiotensin-converting enzyme inhibitors (ACE inhibitors) can increase the risk of hyperkalemia, especially in the presence of renal impairment (renal disease, elderly patients). These agents should be used with caution and serum potassium levels monitored when the substances are coadministered. The Beers Criteria recommends avoiding routine use of this combination in older adults; reserve this combination for patients with demonstrated hypokalemia while taking an ACE inhibitor.
    Captopril; Hydrochlorothiazide, HCTZ: (Major) Amiloride should be used very cautiously with agents that have potential to induce hyperkalemia; serum potassium levels monitored when such agents are coadministered with amiloride. Simultaneous use of a potassium-sparing diuretic (e.g., amiloride) with angiotensin-converting enzyme inhibitors (ACE inhibitors) can increase the risk of hyperkalemia, especially in the presence of renal impairment (renal disease, elderly patients). These agents should be used with caution and serum potassium levels monitored when the substances are coadministered. The Beers Criteria recommends avoiding routine use of this combination in older adults; reserve this combination for patients with demonstrated hypokalemia while taking an ACE inhibitor.
    Carbetapentane; Chlorpheniramine; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Carbetapentane; Diphenhydramine; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Carbetapentane; Guaifenesin; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Carbetapentane; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Carbetapentane; Phenylephrine; Pyrilamine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Carbetapentane; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Carbidopa; Levodopa: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
    Carbidopa; Levodopa; Entacapone: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when amiloride is administered with hydrocodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when amiloride is administered with hydrocodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Carbinoxamine; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Carbinoxamine; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Carbonic anhydrase inhibitors: (Moderate) Carbonic anhydrase inhibitors promote electrolyte excretion including hydrogen ions, sodium, and potassium. They can enhance the sodium depleting effects of other diuretics when used concurrently. Pre-existing hypokalemia and hyperuricemia can also be potentiated by carbonic anhydrase inhibitors. Monitor serum potassium to determine the need for potassium supplementation and alteration in drug therapy.
    Cariprazine: (Moderate) Orthostatic vital signs should be monitored in patients who are at risk for hypotension, such as those receiving cariprazine in combination with antihypertensive agents. Atypical antipsychotics may cause orthostatic hypotension and syncope, most commonly during treatment initiation and dosage increases. Patients should be informed about measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning, or rising slowly from a seated position. Consider a cariprazine dose reduction if hypotension occurs.
    Cetirizine; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Chlophedianol; Guaifenesin; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Chloroprocaine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Chlorpheniramine; Codeine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when a potassium sparing diuretic is administered with codeine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when amiloride is administered with hydrocodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Chlorpheniramine; Hydrocodone: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when amiloride is administered with hydrocodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when amiloride is administered with hydrocodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when amiloride is administered with hydrocodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Chlorpheniramine; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Chlorpheniramine; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Choline Salicylate; Magnesium Salicylate: (Moderate) Salicylates can increase the risk of renal insufficiency in patients receiving diuretics, secondary to effects on renal blood flow. Salicylates inhibit renal prostaglandin production, which causes salt and water retention and decreased renal blood flow. Coadministration may cause hyperkalemia.
    Ciclesonide: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
    Cidofovir: (Severe) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir.
    Citalopram: (Moderate) Citalopram causes dose-dependent QT interval prolongation. Concurrent use of citalopram and medications known to cause electrolyte imbalance may increase the risk of developing QT prolongation. Therefore, caution is advisable during concurrent use of citalopram and diuretics. In addition, patients receiving a diuretic during treatment with citalopram may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of citalopram should be considered in patients who develop symptomatic hyponatremia.
    Clozapine: (Moderate) Clozapine used concomitantly with the antihypertensive agents can increase the risk and severity of hypotension by potentiating the effect of the antihypertensive drug.
    Cocaine: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
    Codeine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when a potassium sparing diuretic is administered with codeine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
    Codeine; Guaifenesin: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when a potassium sparing diuretic is administered with codeine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
    Codeine; Phenylephrine; Promethazine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when a potassium sparing diuretic is administered with codeine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Codeine; Promethazine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when a potassium sparing diuretic is administered with codeine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
    Co-Enzyme Q10, Ubiquinone: (Moderate) Co-enzyme Q10, ubiquinone (CoQ10) may lower blood pressure. CoQ10 use in combination with antihypertensive agents may lead to additional reductions in blood pressure in some individuals. Patients who choose to take CoQ10 concurrently with antihypertensive medications should receive periodic blood pressure monitoring. Patients should be advised to inform their prescriber of their use of CoQ10.
    Conivaptan: (Moderate) There is potential for additive hypotensive effects when conivaptan is coadministered with antihypertensive agents.
    Corticosteroids: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
    Corticotropin, ACTH: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
    Cortisone: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
    Cosyntropin: (Moderate) Use cosyntropin cautiously in patients receiving diuretics. Cosyntropin may accentuate the electrolyte loss associated with diuretic therapy.
    Cyclosporine: (Major) Cyclosporine can cause hyperkalemia. Simultaneous use of cyclosporine with potassium-sparing diuretics, such as amiloride, spironolactone or triamterene, can increase this risk, and is not recommended.
    Darifenacin: (Minor) Diuretics can increase urinary frequency, which may aggravate bladder symptoms.
    Deflazacort: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
    Desloratadine; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Desvenlafaxine: (Moderate) Patients receiving a diuretic during treatment with a Serotonin norepinephrine reuptake inhibitor (SNRI) may be at greater risk of developing hyponatremia and/or the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH may occur during therapy with SNRIs. Cases involving serum sodium levels lower than 110 mmol/L have been reported. Discontinuation of the SNRI should be considered in patients who develop symptomatic hyponatremia.
    Dexamethasone: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Dexmethylphenidate: (Moderate) Dexmethylphenidate can reduce the hypotensive effect of antihypertensive agents, including potassium-sparing diuretics. Periodic evaluation of blood pressure is advisable during concurrent use of dexmethylphenidate and antihypertensive agents, particularly during initial coadministration and after dosage increases of dexmethylphenidate.
    Dextroamphetamine: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like potassium-sparing diuretics. Close monitoring of blood pressure is advised.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Dextromethorphan; Quinidine: (Severe) Seven of ten patients with inducible ventricular tachycardia developed adverse reactions including sustained ventricular tachycardia and other somatic complaints during concomitant amiloride and quinidine administration. The therapeutic antiarrhythmic actions of quinidine were antagonized by amiloride. In addition, quinidine exerts either direct or indirect (alpha-adrenergic blockade) peripheral vasodilatory effects, which can decrease blood pressure. Hypotension is more severe with parenteral quinidine. Until more data are available, this drug combination should be avoided whenever possible.
    Diazoxide: (Moderate) Additive hypotensive effects can occur with the concomitant administration of diazoxide with other antihypertensive agents. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly. The manufacturer advises that IV diazoxide should not be administered to patients within 6 hours of receiving other antihypertensive agents.
    Dichlorphenamide: (Moderate) Use dichlorphenamide and amiloride together with caution as both drugs can cause metabolic acidosis. Concurrent use may increase the severity of metabolic acidosis. Measure sodium bicarbonate concentrations at baseline and periodically during dichlorphenamide treatment. If metabolic acidosis occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy.
    Digoxin: (Moderate) Amiloride can alter the response to digoxin therapy if administered concomitantly. Typically, digoxin concentrations are slightly elevated by amiloride, and a reduced responsiveness to the positive inotropic effects of digoxin therapy has been noted in patients receiving both agents simultaneously. Patients receiving these two drugs concurrently should be monitored for altered responses to digoxin therapy.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when amiloride is administered with hydrocodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Diphenhydramine; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Dofetilide: (Major) Drugs that are actively secreted via cationic tubular secretion, such as amiloride, should be co-administered with caution with dofetilide since they could increase dofetilide plasma concentrations via potential competition for renal cationic secretion. Increased dofetilide plasma concentrations may be associated with proarrhythmias.
    Dolutegravir; Lamivudine: (Moderate) Drugs that are actively secreted via cationic tubular secretion, such as amiloride, should be co-administered with caution with lamivudine since they could increase lamivudine plasma concentrations, and therefore lamivudine associated adverse reactions, via potential competition for renal cationic secretion.
    Donepezil; Memantine: (Minor) Cationic drugs that are eliminated by renal tubular secretion, such as amiloride, may decrease memantine elimination by competing for common renal tubular transport systems. Careful patient monitoring and dose adjustment of memantine and/or amiloride is recommended.
    Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Moderate) Drugs that are actively secreted via cationic tubular secretion, such as amiloride, should be co-administered with caution with lamivudine since they could increase lamivudine plasma concentrations, and therefore lamivudine associated adverse reactions, via potential competition for renal cationic secretion.
    Drospirenone: (Moderate) Drospirenone has antimineralocorticoid effects and may increase serum potassium, therefore concurrent use of potassium-sparing diuretics may increase the risk of hyperkalemia, especially in the presence of renal impairment. Monitor serum potassium during the 1st month of drospirenone treatment if potassium-sparing diuretics are used concurrently and thereafter as clinically indicated. Also monitor for any changes in blood pressure, fluid retention, or renal function.
    Drospirenone; Estradiol: (Moderate) Drospirenone has antimineralocorticoid effects and may increase serum potassium, therefore concurrent use of potassium-sparing diuretics may increase the risk of hyperkalemia, especially in the presence of renal impairment. Monitor serum potassium during the 1st month of drospirenone treatment if potassium-sparing diuretics are used concurrently and thereafter as clinically indicated. Also monitor for any changes in blood pressure, fluid retention, or renal function.
    Drospirenone; Ethinyl Estradiol: (Moderate) Drospirenone has antimineralocorticoid effects and may increase serum potassium, therefore concurrent use of potassium-sparing diuretics may increase the risk of hyperkalemia, especially in the presence of renal impairment. Monitor serum potassium during the 1st month of drospirenone treatment if potassium-sparing diuretics are used concurrently and thereafter as clinically indicated. Also monitor for any changes in blood pressure, fluid retention, or renal function.
    Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) Drospirenone has antimineralocorticoid effects and may increase serum potassium, therefore concurrent use of potassium-sparing diuretics may increase the risk of hyperkalemia, especially in the presence of renal impairment. Monitor serum potassium during the 1st month of drospirenone treatment if potassium-sparing diuretics are used concurrently and thereafter as clinically indicated. Also monitor for any changes in blood pressure, fluid retention, or renal function.
    Duloxetine: (Moderate) Patients receiving a diuretic during treatment with a Serotonin norepinephrine reuptake inhibitor (SNRI) may be at greater risk of developing hyponatremia and/or the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH may occur during therapy with SNRIs. Cases involving serum sodium levels lower than 110 mmol/L have been reported. Discontinuation of the SNRI should be considered in patients who develop symptomatic hyponatremia.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Drugs that are actively secreted via cationic tubular secretion, such as amiloride, should be co-administered with caution with lamivudine since they could increase lamivudine plasma concentrations, and therefore lamivudine associated adverse reactions, via potential competition for renal cationic secretion.
    Empagliflozin: (Moderate) Administer empagliflozin; metformin with caution in patients receiving diuretics. When empagliflozin is initiated in patients already receiving diuretics, volume depletion can occur. Patients with impaired renal function, low systolic blood pressure, or who are elderly may also be at a greater risk for volume depletion and perhaps symptomatic hypotension. Before initiating empagliflozin in patients with one or more of these characteristics, assess volume status and correct if necessary. Monitor for signs and symptoms after initiating therapy.
    Empagliflozin; Linagliptin: (Moderate) Administer empagliflozin; metformin with caution in patients receiving diuretics. When empagliflozin is initiated in patients already receiving diuretics, volume depletion can occur. Patients with impaired renal function, low systolic blood pressure, or who are elderly may also be at a greater risk for volume depletion and perhaps symptomatic hypotension. Before initiating empagliflozin in patients with one or more of these characteristics, assess volume status and correct if necessary. Monitor for signs and symptoms after initiating therapy.
    Empagliflozin; Metformin: (Moderate) Administer empagliflozin; metformin with caution in patients receiving diuretics. When empagliflozin is initiated in patients already receiving diuretics, volume depletion can occur. Patients with impaired renal function, low systolic blood pressure, or who are elderly may also be at a greater risk for volume depletion and perhaps symptomatic hypotension. Before initiating empagliflozin in patients with one or more of these characteristics, assess volume status and correct if necessary. Monitor for signs and symptoms after initiating therapy.
    Enalapril, Enalaprilat: (Major) Amiloride should be used very cautiously with agents that have potential to induce hyperkalemia; serum potassium levels monitored when such agents are coadministered with amiloride. Simultaneous use of a potassium-sparing diuretic (e.g., amiloride) with angiotensin-converting enzyme inhibitors (ACE inhibitors) can increase the risk of hyperkalemia, especially in the presence of renal impairment (renal disease, elderly patients). These agents should be used with caution and serum potassium levels monitored when the substances are coadministered. The Beers Criteria recommends avoiding routine use of this combination in older adults; reserve this combination for patients with demonstrated hypokalemia while taking an ACE inhibitor.
    Enalapril; Felodipine: (Major) Amiloride should be used very cautiously with agents that have potential to induce hyperkalemia; serum potassium levels monitored when such agents are coadministered with amiloride. Simultaneous use of a potassium-sparing diuretic (e.g., amiloride) with angiotensin-converting enzyme inhibitors (ACE inhibitors) can increase the risk of hyperkalemia, especially in the presence of renal impairment (renal disease, elderly patients). These agents should be used with caution and serum potassium levels monitored when the substances are coadministered. The Beers Criteria recommends avoiding routine use of this combination in older adults; reserve this combination for patients with demonstrated hypokalemia while taking an ACE inhibitor.
    Enalapril; Hydrochlorothiazide, HCTZ: (Major) Amiloride should be used very cautiously with agents that have potential to induce hyperkalemia; serum potassium levels monitored when such agents are coadministered with amiloride. Simultaneous use of a potassium-sparing diuretic (e.g., amiloride) with angiotensin-converting enzyme inhibitors (ACE inhibitors) can increase the risk of hyperkalemia, especially in the presence of renal impairment (renal disease, elderly patients). These agents should be used with caution and serum potassium levels monitored when the substances are coadministered. The Beers Criteria recommends avoiding routine use of this combination in older adults; reserve this combination for patients with demonstrated hypokalemia while taking an ACE inhibitor.
    Enflurane: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Entecavir: (Moderate) Both entecavir and amiloride are secreted by active tubular secretion. In theory, coadministration of entecavir with amiloride may increase the serum concentrations of either drug due to competition for the drug elimination pathway. The manufacturer of entecavir recommends monitoring for adverse effects when these drugs are coadministered.
    Ephedrine: (Major) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by potassium-sparing diuretics. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved.
    Eplerenone: (Severe) Eplerenone should not be used concomitantly with potassium-sparing diuretics (e.g., amiloride, spironolactone, triamterene) because of the increased risk of developing hyperkalemia. The combine use of these medications in patients with hypertension or renal impairment contraindicated.
    Epoprostenol: (Moderate) Epoprostenol can have additive effects when administered with other antihypertensive agents. These effects can be used to therapeutic advantage, but dosage adjustments may be necessary.
    Eprosartan: (Major) Potassium-sparing diuretics, such as amiloride, should be used with caution in patients taking drugs that may increase serum potassium levels such as angiotensin II receptor antagonists. Concurrent use can cause hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
    Eprosartan; Hydrochlorothiazide, HCTZ: (Major) Potassium-sparing diuretics, such as amiloride, should be used with caution in patients taking drugs that may increase serum potassium levels such as angiotensin II receptor antagonists. Concurrent use can cause hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
    Escitalopram: (Moderate) Patients receiving a diuretic during treatment with escitalopram may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of escitalopram should be considered in patients who develop symptomatic hyponatremia.
    Estradiol Cypionate; Medroxyprogesterone: (Minor) Estrogens can induce fluid retention and may increase blood pressure in some patients; patients who are receiving antihypertensive agents concurrently with hormone therapy should be monitored for antihypertensive effectiveness.
    Estradiol: (Minor) Estrogens can induce fluid retention and may increase blood pressure in some patients; patients who are receiving antihypertensive agents concurrently with hormone therapy should be monitored for antihypertensive effectiveness.
    Etomidate: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Fentanyl: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when diuretics are administered with fentanyl. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
    Fexofenadine; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Fish Oil, Omega-3 Fatty Acids (Dietary Supplements): (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
    Fludrocortisone: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
    Flunisolide: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
    Fluoxetine: (Moderate) Patients receiving a diuretic during treatment with fluoxetine may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of fluoxetine should be considered in patients who develop symptomatic hyponatremia.
    Fluoxetine; Olanzapine: (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents. (Moderate) Patients receiving a diuretic during treatment with fluoxetine may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of fluoxetine should be considered in patients who develop symptomatic hyponatremia.
    Fluticasone: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
    Fluticasone; Salmeterol: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
    Fluticasone; Umeclidinium; Vilanterol: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
    Fluticasone; Vilanterol: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
    Fluvoxamine: (Moderate) Patients receiving a diuretic during treatment with fluvoxamine may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/L have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of fluvoxamine should be considered in patients who develop symptomatic hyponatremia.
    Formoterol; Mometasone: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
    Fosinopril: (Major) Amiloride should be used very cautiously with agents that have potential to induce hyperkalemia; serum potassium levels monitored when such agents are coadministered with amiloride. Simultaneous use of a potassium-sparing diuretic (e.g., amiloride) with angiotensin-converting enzyme inhibitors (ACE inhibitors) can increase the risk of hyperkalemia, especially in the presence of renal impairment (renal disease, elderly patients). These agents should be used with caution and serum potassium levels monitored when the substances are coadministered. The Beers Criteria recommends avoiding routine use of this combination in older adults; reserve this combination for patients with demonstrated hypokalemia while taking an ACE inhibitor.
    Fosinopril; Hydrochlorothiazide, HCTZ: (Major) Amiloride should be used very cautiously with agents that have potential to induce hyperkalemia; serum potassium levels monitored when such agents are coadministered with amiloride. Simultaneous use of a potassium-sparing diuretic (e.g., amiloride) with angiotensin-converting enzyme inhibitors (ACE inhibitors) can increase the risk of hyperkalemia, especially in the presence of renal impairment (renal disease, elderly patients). These agents should be used with caution and serum potassium levels monitored when the substances are coadministered. The Beers Criteria recommends avoiding routine use of this combination in older adults; reserve this combination for patients with demonstrated hypokalemia while taking an ACE inhibitor.
    Fospropofol: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Gallium Ga 68 Dotatate: (Major) Avoid use of other diuretics with mannitol, if possible. Concomitant administration may potentiate the renal toxicity of mannitol.
    General anesthetics: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Guaifenesin; Hydrocodone: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when amiloride is administered with hydrocodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when amiloride is administered with hydrocodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Guaifenesin; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Guaifenesin; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Haloperidol: (Moderate) In general, haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
    Halothane: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Heparin: (Moderate) Simultaneous use of a potassium-sparing diuretic with heparin can increase the risk of hyperkalemia, especially in the presence of renal impairment. Monitoring of serum potassium is recommended as indicated.
    Homatropine; Hydrocodone: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when amiloride is administered with hydrocodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
    Hydralazine; Isosorbide Dinitrate, ISDN: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
    Hydrochlorothiazide, HCTZ; Irbesartan: (Major) Potassium-sparing diuretics, such as amiloride, should be used with caution in patients taking drugs that may increase serum potassium levels such as angiotensin II receptor antagonists. Concurrent use can cause hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
    Hydrochlorothiazide, HCTZ; Lisinopril: (Major) Amiloride should be used very cautiously with agents that have potential to induce hyperkalemia; serum potassium levels monitored when such agents are coadministered with amiloride. Simultaneous use of a potassium-sparing diuretic (e.g., amiloride) with angiotensin-converting enzyme inhibitors (ACE inhibitors) can increase the risk of hyperkalemia, especially in the presence of renal impairment (renal disease, elderly patients). These agents should be used with caution and serum potassium levels monitored when the substances are coadministered. The Beers Criteria recommends avoiding routine use of this combination in older adults; reserve this combination for patients with demonstrated hypokalemia while taking an ACE inhibitor.
    Hydrochlorothiazide, HCTZ; Losartan: (Major) Potassium-sparing diuretics, such as amiloride, should be used with caution in patients taking drugs that may increase serum potassium levels such as angiotensin II receptor antagonists. Concurrent use can cause hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
    Hydrochlorothiazide, HCTZ; Moexipril: (Major) Amiloride should be used very cautiously with agents that have potential to induce hyperkalemia; serum potassium levels monitored when such agents are coadministered with amiloride. Simultaneous use of a potassium-sparing diuretic (e.g., amiloride) with angiotensin-converting enzyme inhibitors (ACE inhibitors) can increase the risk of hyperkalemia, especially in the presence of renal impairment (renal disease, elderly patients). These agents should be used with caution and serum potassium levels monitored when the substances are coadministered. The Beers Criteria recommends avoiding routine use of this combination in older adults; reserve this combination for patients with demonstrated hypokalemia while taking an ACE inhibitor.
    Hydrochlorothiazide, HCTZ; Olmesartan: (Major) Potassium-sparing diuretics, such as amiloride, should be used with caution in patients taking drugs that may increase serum potassium levels such as angiotensin II receptor antagonists. Concurrent use can cause hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
    Hydrochlorothiazide, HCTZ; Quinapril: (Major) Amiloride should be used very cautiously with agents that have potential to induce hyperkalemia; serum potassium levels monitored when such agents are coadministered with amiloride. Simultaneous use of a potassium-sparing diuretic (e.g., amiloride) with angiotensin-converting enzyme inhibitors (ACE inhibitors) can increase the risk of hyperkalemia, especially in the presence of renal impairment (renal disease, elderly patients). These agents should be used with caution and serum potassium levels monitored when the substances are coadministered. The Beers Criteria recommends avoiding routine use of this combination in older adults; reserve this combination for patients with demonstrated hypokalemia while taking an ACE inhibitor.
    Hydrochlorothiazide, HCTZ; Telmisartan: (Major) Potassium-sparing diuretics, such as amiloride, should be used with caution in patients taking drugs that may increase serum potassium levels such as angiotensin II receptor antagonists. Concurrent use can cause hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
    Hydrochlorothiazide, HCTZ; Valsartan: (Major) Potassium-sparing diuretics, such as amiloride, should be used with caution in patients taking drugs that may increase serum potassium levels such as angiotensin II receptor antagonists. Concurrent use can cause hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
    Hydrocodone: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when amiloride is administered with hydrocodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
    Hydrocodone; Ibuprofen: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when amiloride is administered with hydrocodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
    Hydrocodone; Phenylephrine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when amiloride is administered with hydrocodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Hydrocodone; Potassium Guaiacolsulfonate: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when amiloride is administered with hydrocodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when amiloride is administered with hydrocodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Hydrocodone; Pseudoephedrine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when amiloride is administered with hydrocodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Hydrocortisone: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
    Hydromorphone: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when amiloride is administered with hydromorphone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
    Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Salicylates can increase the risk of renal insufficiency in patients receiving diuretics, secondary to effects on renal blood flow. Salicylates inhibit renal prostaglandin production, which causes salt and water retention and decreased renal blood flow. Coadministration may cause hyperkalemia.
    Ibuprofen lysine: (Moderate) Ibuprofen lysine may reduce the effect of diuretics; diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated patients. During coadministration of NSAIDs and diuretic therapy, patients should be monitored for changes in the effectiveness of their diuretic therapy and for signs and symptoms of renal impairment.
    Ibuprofen; Oxycodone: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when amiloride is administered with oxycodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
    Ibuprofen; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Iloperidone: (Moderate) Secondary to alpha-blockade, iloperidone can produce vasodilation that may result in additive effects during concurrent use with antihypertensive agents. The potential reduction in blood pressure can precipitate orthostatic hypotension and associated dizziness, tachycardia, and syncope. If concurrent use of iloperidone and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known.
    Iloprost: (Moderate) Amiloride can have additive effects when administered with other antihypertensive agents. These effects can be used to therapeutic advantage, but dosage adjustments may be necessary.
    Inamrinone: (Moderate) Hypokalemia may occur due to excessive diuresis during inamrinone therapy. Fluid and electrolyte changes and renal function should be carefully monitored during inamrinone therapy.
    Indapamide: (Moderate) The effects of indapamide may be additive when administered with other antihypertensive agents or diuretics. This may be desirable, but occasionally orthostatic hypotension may occur. Dosages should be adjusted based on clinical response.
    Inotersen: (Moderate) Use caution with concomitant use of inotersen and diuretics due to the risk of glomerulonephritis and nephrotoxicity.
    Intravenous Lipid Emulsions: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
    Irbesartan: (Major) Potassium-sparing diuretics, such as amiloride, should be used with caution in patients taking drugs that may increase serum potassium levels such as angiotensin II receptor antagonists. Concurrent use can cause hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
    Isocarboxazid: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Isoflurane: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Isoproterenol: (Moderate) The pharmacologic effects of isoproterenol may cause an increase in blood pressure. If isoproterenol is used concomitantly with antihypertensives, the blood pressure should be monitored as the administration of isoproterenol can compromise the effectiveness of antihypertensive agents.
    Isosorbide Dinitrate, ISDN: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
    Isosorbide Mononitrate: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
    Ketamine: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Lamivudine, 3TC: (Moderate) Drugs that are actively secreted via cationic tubular secretion, such as amiloride, should be co-administered with caution with lamivudine since they could increase lamivudine plasma concentrations, and therefore lamivudine associated adverse reactions, via potential competition for renal cationic secretion.
    Lamivudine, 3TC; Zidovudine, ZDV: (Moderate) Drugs that are actively secreted via cationic tubular secretion, such as amiloride, should be co-administered with caution with lamivudine since they could increase lamivudine plasma concentrations, and therefore lamivudine associated adverse reactions, via potential competition for renal cationic secretion.
    Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Drugs that are actively secreted via cationic tubular secretion, such as amiloride, should be co-administered with caution with lamivudine since they could increase lamivudine plasma concentrations, and therefore lamivudine associated adverse reactions, via potential competition for renal cationic secretion.
    Levodopa: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
    Levomilnacipran: (Moderate) Patients receiving a diuretic during treatment with a Serotonin norepinephrine reuptake inhibitor (SNRI) may be at greater risk of developing hyponatremia and/or the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH may occur during therapy with SNRIs. Cases involving serum sodium levels lower than 110 mmol/L have been reported. Discontinuation of the SNRI should be considered in patients who develop symptomatic hyponatremia.
    Levorphanol: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when amiloride is administered with levorphanol. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
    Lisdexamfetamine: (Minor) Lisedexamfetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like potassium-sparing diuretics. Close monitoring of blood pressure is advised.
    Lisinopril: (Major) Amiloride should be used very cautiously with agents that have potential to induce hyperkalemia; serum potassium levels monitored when such agents are coadministered with amiloride. Simultaneous use of a potassium-sparing diuretic (e.g., amiloride) with angiotensin-converting enzyme inhibitors (ACE inhibitors) can increase the risk of hyperkalemia, especially in the presence of renal impairment (renal disease, elderly patients). These agents should be used with caution and serum potassium levels monitored when the substances are coadministered. The Beers Criteria recommends avoiding routine use of this combination in older adults; reserve this combination for patients with demonstrated hypokalemia while taking an ACE inhibitor.
    Lithium: (Minor) The risk of lithium toxicity may be increased in patients receiving medications that affect kidney function and sodium excretion, such as diuretics. However, concurrent use of potassium-sparing diuretics (e.g., amiloride, spironolactone, triamterene) with lithium is generally regarded as safe. Lithium is primarily reabsorbed from the proximal tubules whereas potassium-sparing diuretics inhibit the endothelial sodium channel in the renal collecting duct thereby inhibiting reabsorption of sodium and lithium. In one small study evaluating concurrent use of lithium and spironolactone, lithium clearance was increased by 16%, which was not considered clinically significant. Amiloride has been safely used as a reversal agent for lithium-induced nephrogenic diabetes insipidus. There is a lack of evidence to evaluate the effect of lithium and triamterene co-administration, however, a significant interaction would not be expected due to the pharmacologic similarities with other potassium-sparing diuretics.
    Loratadine; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Losartan: (Major) Potassium-sparing diuretics, such as amiloride, should be used with caution in patients taking drugs that may increase serum potassium levels such as angiotensin II receptor antagonists. Concurrent use can cause hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
    Lovastatin; Niacin: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
    Lurasidone: (Moderate) Due to the antagonism of lurasidone at alpha-1 adrenergic receptors, the drug may enhance the hypotensive effects of alpha-blockers and other antihypertensive agents. If concurrent use of lurasidone and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known.
    Magnesium Citrate: (Moderate) The use of saline laxatives (e.g., magnesium citrate) with potassium-sparing diuretics may interfere with the potassium-sparing effect of such diuretics due to excess fluid and electrolyte loss. In addition, potassium-sparing diuretics may interfere with the kidneys ability to regulate magnesium concentrations; long-term use of potassium-sparing diuretics has been found to increase renal tubular reabsorption of magnesium which may cause hypermagnesemia, especially in patients with renal insufficiency.
    Magnesium Hydroxide: (Moderate) Long-term use of potassium-sparing diuretics has been found to increase renal tubular reabsorption of magnesium which may cause hypermagnesemia in patients also receiving magnesium supplements, especially in patients with renal insufficiency.
    Magnesium Salicylate: (Moderate) Salicylates can increase the risk of renal insufficiency in patients receiving diuretics, secondary to effects on renal blood flow. Salicylates inhibit renal prostaglandin production, which causes salt and water retention and decreased renal blood flow. Coadministration may cause hyperkalemia.
    Magnesium Salts: (Moderate) Long-term use of potassium-sparing diuretics has been found to increase renal tubular reabsorption of magnesium which may cause hypermagnesemia in patients also receiving magnesium supplements, especially in patients with renal insufficiency. (Moderate) Long-term use of potassium-sparing diuretics has been found to increase renal tubular reabsorption of magnesium which may cause hypermagnesemia in patients also receiving magnesium supplements, especially in patients with renal insufficiency. In addition, use caution when prescribing sulfate salt bowel preps in patients taking medications that may affect renal function such as diuretics.
    Magnesium Sulfate; Potassium Sulfate; Sodium Sulfate: (Moderate) Use caution when prescribing sulfate salt bowel preparation in patients taking concomitant medications that may affect renal function such as diuretics.
    Mannitol: (Major) Avoid use of other diuretics with mannitol, if possible. Concomitant administration may potentiate the renal toxicity of mannitol.
    Memantine: (Minor) Cationic drugs that are eliminated by renal tubular secretion, such as amiloride, may decrease memantine elimination by competing for common renal tubular transport systems. Careful patient monitoring and dose adjustment of memantine and/or amiloride is recommended.
    Meperidine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when amiloride is administered with meperidine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
    Meperidine; Promethazine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when amiloride is administered with meperidine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
    Mestranol; Norethindrone: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients; monitor patients receiving concurrent therapy to confirm that the desired antihypertensive effect is being obtained.
    Methadone: (Moderate) Diuretics can cause electrolyte disturbances such as hypomagnesemia and hypokalemia, which may prolong the QT interval. As methadone may also prolong the QT interval, cautious coadministration with diuretics is needed. Also opiate agonists may potentiate orthostatic hypotension when given concomitantly with spironolactone.
    Methamphetamine: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, like potassium-sparing diuretics. Close monitoring of blood pressure is advised.
    Methazolamide: (Moderate) Carbonic anhydrase inhibitors promote electrolyte excretion including hydrogen ions, sodium, and potassium. They can enhance the sodium depleting effects of other diuretics when used concurrently. Pre-existing hypokalemia and hyperuricemia can also be potentiated by carbonic anhydrase inhibitors. Monitor serum potassium to determine the need for potassium supplementation and alteration in drug therapy.
    Methohexital: (Moderate) Concurrent use of methohexital and antihypertensive agents increases the risk of developing hypotension.
    Methylphenidate: (Minor) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate. Methylphenidate can reduce the hypotensive effect of antihypertensive agents such as potassium-sparing diuretics.
    Methylprednisolone: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
    Milnacipran: (Moderate) Patients receiving a diuretic during treatment with a Serotonin norepinephrine reuptake inhibitor (SNRI) may be at greater risk of developing hyponatremia and/or the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH may occur during therapy with SNRIs. Cases involving serum sodium levels lower than 110 mmol/L have been reported. Discontinuation of the SNRI should be considered in patients who develop symptomatic hyponatremia.
    Milrinone: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
    Mirtazapine: (Moderate) Hyponatremia has been reported very rarely during mirtazapine administration. Caution is advisable in patients receiving medications known to cause hyponatremia, such as diuretics. Hyponatremia may manifest as headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness which may result in falls. Severe manifestations include hallucinations, syncope, seizure, coma, respiratory arrest, and death. Symptomatic hyponatremia may require discontinuation of mirtazapine, as well as implementation of the appropriate medical interventions.
    Moexipril: (Major) Amiloride should be used very cautiously with agents that have potential to induce hyperkalemia; serum potassium levels monitored when such agents are coadministered with amiloride. Simultaneous use of a potassium-sparing diuretic (e.g., amiloride) with angiotensin-converting enzyme inhibitors (ACE inhibitors) can increase the risk of hyperkalemia, especially in the presence of renal impairment (renal disease, elderly patients). These agents should be used with caution and serum potassium levels monitored when the substances are coadministered. The Beers Criteria recommends avoiding routine use of this combination in older adults; reserve this combination for patients with demonstrated hypokalemia while taking an ACE inhibitor.
    Mometasone: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
    Morphine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when a potassium-sparing diuretic is administered with morphine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. Morphine may also cause acute urinary retention by causing a spasm of the bladder sphincter; men with enlarged prostates may have a higher risk of this reaction.
    Morphine; Naltrexone: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when a potassium-sparing diuretic is administered with morphine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. Morphine may also cause acute urinary retention by causing a spasm of the bladder sphincter; men with enlarged prostates may have a higher risk of this reaction.
    Naproxen; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Nebivolol; Valsartan: (Major) Potassium-sparing diuretics, such as amiloride, should be used with caution in patients taking drugs that may increase serum potassium levels such as angiotensin II receptor antagonists. Concurrent use can cause hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
    Nefazodone: (Minor) Although relatively infrequent, nefazodone may cause orthostatic hypotension in some patients; this effect may be additive with antihypertensive agents. Blood pressure monitoring and dosage adjustments of either drug may be necessary.
    Nesiritide, BNP: (Major) The potential for hypotension may be increased when coadministering nesiritide with antihypertensive agents.
    Niacin, Niacinamide: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
    Niacin; Simvastatin: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
    Nitrates: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
    Nitroglycerin: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
    Nitroprusside: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
    Nonsteroidal antiinflammatory drugs: (Moderate) Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the natriuretic effect of diuretics in some patients. NSAIDS have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. Patients taking diuretics and NSAIDS concurrently are at higher risk of developing renal insufficiency. If an NSAID and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy.
    Octreotide: (Moderate) Patients receiving diuretics or other agents to control fluid and electrolyte balance may require dosage adjustments while receiving octreotide due to additive effects.
    Olanzapine: (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents.
    Olmesartan: (Major) Potassium-sparing diuretics, such as amiloride, should be used with caution in patients taking drugs that may increase serum potassium levels such as angiotensin II receptor antagonists. Concurrent use can cause hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
    Oxybutynin: (Minor) Diuretics can increase urinary frequency, which may aggravate bladder symptoms.
    Oxycodone: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when amiloride is administered with oxycodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
    Oxymetazoline: (Major) The vasoconstricting actions of oxymetazoline, an alpha adrenergic agonist, may reduce the antihypertensive effects produced by diuretics. If these drugs are used together, closely monitor for changes in blood pressure.
    Oxymorphone: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when potassium-sparring diuretics are administered with oxymorphone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
    Paliperidone: (Moderate) Paliperidone may cause orthostatic hypotension, thereby enhancing the hypotensive effects of antihypertensive agents. Orthostatic vital signs should be monitored in patients receiving paliperidone and potassium-sparing diuretics who are susceptible to hypotension.
    Paroxetine: (Moderate) Patients receiving a diuretic during treatment with paroxetine may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of paroxetine should be considered in patients who develop symptomatic hyponatremia.
    Penicillin G: (Major) Concomitant use of high doses of parenteral penicillin G potassium with potassium-sparing diuretics can cause hyperkalemia.
    Pentazocine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when potassium-sparring diuretics are administered with pentazocine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
    Pentazocine; Naloxone: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when potassium-sparring diuretics are administered with pentazocine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
    Pentoxifylline: (Moderate) Pentoxifylline has been used concurrently with antihypertensive drugs (beta blockers, diuretics) without observed problems. Small decreases in blood pressure have been observed in some patients treated with pentoxifylline; periodic systemic blood pressure monitoring is recommended for patients receiving concomitant antihypertensives. If indicated, dosage of the antihypertensive agents should be reduced.
    Perindopril: (Major) Amiloride should be used very cautiously with agents that have potential to induce hyperkalemia; serum potassium levels monitored when such agents are coadministered with amiloride. Simultaneous use of a potassium-sparing diuretic (e.g., amiloride) with angiotensin-converting enzyme inhibitors (ACE inhibitors) can increase the risk of hyperkalemia, especially in the presence of renal impairment (renal disease, elderly patients). These agents should be used with caution and serum potassium levels monitored when the substances are coadministered. The Beers Criteria recommends avoiding routine use of this combination in older adults; reserve this combination for patients with demonstrated hypokalemia while taking an ACE inhibitor.
    Perindopril; Amlodipine: (Major) Amiloride should be used very cautiously with agents that have potential to induce hyperkalemia; serum potassium levels monitored when such agents are coadministered with amiloride. Simultaneous use of a potassium-sparing diuretic (e.g., amiloride) with angiotensin-converting enzyme inhibitors (ACE inhibitors) can increase the risk of hyperkalemia, especially in the presence of renal impairment (renal disease, elderly patients). These agents should be used with caution and serum potassium levels monitored when the substances are coadministered. The Beers Criteria recommends avoiding routine use of this combination in older adults; reserve this combination for patients with demonstrated hypokalemia while taking an ACE inhibitor.
    Phenelzine: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Phenylephrine; Promethazine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Polyethylene Glycol; Electrolytes: (Moderate) Use caution when prescribing sulfate salt bowel preparation in patients taking concomitant medications that may affect renal function such as diuretics.
    Polyethylene Glycol; Electrolytes; Ascorbic Acid: (Moderate) Use caution when prescribing sulfate salt bowel preparation in patients taking concomitant medications that may affect renal function such as diuretics.
    Potassium: (Severe) Concomitant use of potassium supplements and amiloride is contraindicated. Coadministration may result in severe hyperkalemia.
    Prazosin: (Moderate) Prazosin is well-known to produce a 'first-dose' phenomenon. Some patients develop significant hypotension shortly after administration of the first dose. The first dose response (acute postural hypotension) of prazosin may be exaggerated in patients who are receiving beta-adrenergic blockers, diuretics, or other antihypertensive agents. Concomitant administration of prazosin with other antihypertensive agents is not prohibited, however. This can be therapeutically advantageous, but lower dosages of each agent should be used.
    Prednisolone: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
    Prednisone: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
    Procainamide: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Procaine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Propofol: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Quinapril: (Major) Amiloride should be used very cautiously with agents that have potential to induce hyperkalemia; serum potassium levels monitored when such agents are coadministered with amiloride. Simultaneous use of a potassium-sparing diuretic (e.g., amiloride) with angiotensin-converting enzyme inhibitors (ACE inhibitors) can increase the risk of hyperkalemia, especially in the presence of renal impairment (renal disease, elderly patients). These agents should be used with caution and serum potassium levels monitored when the substances are coadministered. The Beers Criteria recommends avoiding routine use of this combination in older adults; reserve this combination for patients with demonstrated hypokalemia while taking an ACE inhibitor.
    Quinidine: (Severe) Seven of ten patients with inducible ventricular tachycardia developed adverse reactions including sustained ventricular tachycardia and other somatic complaints during concomitant amiloride and quinidine administration. The therapeutic antiarrhythmic actions of quinidine were antagonized by amiloride. In addition, quinidine exerts either direct or indirect (alpha-adrenergic blockade) peripheral vasodilatory effects, which can decrease blood pressure. Hypotension is more severe with parenteral quinidine. Until more data are available, this drug combination should be avoided whenever possible.
    Ramipril: (Major) Amiloride should be used very cautiously with agents that have potential to induce hyperkalemia; serum potassium levels monitored when such agents are coadministered with amiloride. Simultaneous use of a potassium-sparing diuretic (e.g., amiloride) with angiotensin-converting enzyme inhibitors (ACE inhibitors) can increase the risk of hyperkalemia, especially in the presence of renal impairment (renal disease, elderly patients). These agents should be used with caution and serum potassium levels monitored when the substances are coadministered. The Beers Criteria recommends avoiding routine use of this combination in older adults; reserve this combination for patients with demonstrated hypokalemia while taking an ACE inhibitor.
    Rasagiline: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Risperidone: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
    Sacubitril; Valsartan: (Major) Potassium-sparing diuretics, such as amiloride, should be used with caution in patients taking drugs that may increase serum potassium levels such as angiotensin II receptor antagonists. Concurrent use can cause hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
    Salicylates: (Moderate) Salicylates can increase the risk of renal insufficiency in patients receiving diuretics, secondary to effects on renal blood flow. Salicylates inhibit renal prostaglandin production, which causes salt and water retention and decreased renal blood flow. Coadministration may cause hyperkalemia.
    Salsalate: (Moderate) Salicylates can increase the risk of renal insufficiency in patients receiving diuretics, secondary to effects on renal blood flow. Salicylates inhibit renal prostaglandin production, which causes salt and water retention and decreased renal blood flow. Coadministration may cause hyperkalemia.
    Selegiline: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Serotonin norepinephrine reuptake inhibitors: (Moderate) Patients receiving a diuretic during treatment with a Serotonin norepinephrine reuptake inhibitor (SNRI) may be at greater risk of developing hyponatremia and/or the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH may occur during therapy with SNRIs. Cases involving serum sodium levels lower than 110 mmol/L have been reported. Discontinuation of the SNRI should be considered in patients who develop symptomatic hyponatremia.
    Sertraline: (Moderate) Patients receiving a diuretic during treatment with sertraline may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of sertraline should be considered in patients who develop symptomatic hyponatremia.
    Sevoflurane: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Silodosin: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Sodium Phosphate Monobasic Monohydrate; Sodium Phosphate Dibasic Anhydrous: (Moderate) Concomitant use of medicines with potential to alter renal perfusion or function such as diuretics may increase the risk of acute phosphate nephropathy in patients receiving sodium phosphate monobasic monohydrate; sodium phosphate dibasic anhydrous.
    Sodium picosulfate; Magnesium oxide; Anhydrous citric acid: (Moderate) Use caution when prescribing sodium picosulfate; magnesium oxide; anhydrous citric acid in patients taking concomitant medications that may affect renal function such as diuretics. In addition, use caution in patients receiving drugs where hypokalemia is a particular risk.
    Solifenacin: (Minor) Diuretics can increase urinary frequency, which may aggravate bladder symptoms. Risk versus benefit should be addressed in patients receiving diuretics and solifenacin.
    Streptozocin: (Minor) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents (e.g,. aminoglycosides, amphotericin B, cisplatin, foscarnet, or diuretics) could exacerbate the renal insult.
    Sufentanil: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when amiloride is administered with sufentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
    Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Major) Trimethoprim has a potassium-sparing effect and may induce hyperkalemia, especially in patients with pre-existing risk factors for hyperkalemia (e.g., renal disease). Patients, especially those with renal dysfunction, should be carefully monitored for hyperkalemia during concomitant use of potassium-sparing diuretics and trimethoprim.
    Tacrolimus: (Major) Simultaneous use of a potassium-sparing diuretic with tacrolimus can increase the risk of hyperkalemia, and is generally not recommended. If these drugs are used concomitantly, serum potassium should be monitored frequently.
    Tapentadol: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when potassium-sparing diuretics are administered with tapentadol. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
    Telmisartan: (Major) Potassium-sparing diuretics, such as amiloride, should be used with caution in patients taking drugs that may increase serum potassium levels such as angiotensin II receptor antagonists. Concurrent use can cause hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
    Tetrabenazine: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Tetracaine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Use extreme caution with the concomitant use of tetracaine and antihypertensive agents.
    Thiopental: (Moderate) Concurrent use of thiopental and alpha-blockers or antihypertensive agents increases the risk of developing hypotension.
    Thiothixene: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Tizanidine: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
    Tolterodine: (Minor) Diuretics can increase urinary frequency, which may aggravate bladder symptoms.
    Tolvaptan: (Moderate) Monitor serum potassium closely if tolvaptan and potassium-sparing diuretics are used together. In clinical studies, hyperkalemia was reported at a rate 1% to 2% higher when tolvaptan was administered with potassium-sparing diuretics than when potassium-sparing diuretics were administered with placebo.
    Tramadol: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when potassium-sparing diuretics are administered with tramadol. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
    Trandolapril: (Major) Amiloride should be used very cautiously with agents that have potential to induce hyperkalemia; serum potassium levels monitored when such agents are coadministered with amiloride. Simultaneous use of a potassium-sparing diuretic (e.g., amiloride) with angiotensin-converting enzyme inhibitors (ACE inhibitors) can increase the risk of hyperkalemia, especially in the presence of renal impairment (renal disease, elderly patients). These agents should be used with caution and serum potassium levels monitored when the substances are coadministered. The Beers Criteria recommends avoiding routine use of this combination in older adults; reserve this combination for patients with demonstrated hypokalemia while taking an ACE inhibitor.
    Trandolapril; Verapamil: (Major) Amiloride should be used very cautiously with agents that have potential to induce hyperkalemia; serum potassium levels monitored when such agents are coadministered with amiloride. Simultaneous use of a potassium-sparing diuretic (e.g., amiloride) with angiotensin-converting enzyme inhibitors (ACE inhibitors) can increase the risk of hyperkalemia, especially in the presence of renal impairment (renal disease, elderly patients). These agents should be used with caution and serum potassium levels monitored when the substances are coadministered. The Beers Criteria recommends avoiding routine use of this combination in older adults; reserve this combination for patients with demonstrated hypokalemia while taking an ACE inhibitor.
    Tranylcypromine: (Severe) The use of hypotensive agents and tranylcypromine is contraindicated by the manufacturer of tranylcypromine because the effects of hypotensive agents may be markedly potentiated.
    Trazodone: (Minor) Due to additive hypotensive effects, patients receiving antihypertensive agents concurrently with trazodone may have excessive hypotension. Decreased dosage of the antihypertensive agent may be required when given with trazodone.
    Triamcinolone: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
    Trimethoprim: (Major) Trimethoprim has a potassium-sparing effect and may induce hyperkalemia, especially in patients with pre-existing risk factors for hyperkalemia (e.g., renal disease). Patients, especially those with renal dysfunction, should be carefully monitored for hyperkalemia during concomitant use of potassium-sparing diuretics and trimethoprim.
    Trospium: (Minor) Amiloride is actively secreted via cationic tubular secretion and may decrease trospium elimination by competing for common renal tubular transport systems. Careful patient monitoring and dose adjustments of both drugs, if needed, is recommended.
    Valsartan: (Major) Potassium-sparing diuretics, such as amiloride, should be used with caution in patients taking drugs that may increase serum potassium levels such as angiotensin II receptor antagonists. Concurrent use can cause hyperkalemia, especially in elderly patients or patients with impaired renal function. Coadministration may also result in increases in serum creatinine in heart failure patients.
    Venlafaxine: (Moderate) Patients receiving a diuretic during treatment with a Serotonin norepinephrine reuptake inhibitor (SNRI) may be at greater risk of developing hyponatremia and/or the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH may occur during therapy with SNRIs. Cases involving serum sodium levels lower than 110 mmol/L have been reported. Discontinuation of the SNRI should be considered in patients who develop symptomatic hyponatremia.
    Vilazodone: (Moderate) Patients receiving vilazodone with medications known to cause hyponatremia, such as diuretics, may be at increased risk of developing hyponatremia. Hyponatremia has occurred in association with the use of antidepressants such as selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), and mirtazapine. Hyponatremia may manifest as headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness which may result in falls. Severe manifestations include hallucinations, syncope, seizure, coma, respiratory arrest, and death. Symptomatic hyponatremia may require discontinuation of vilazodone, as well as implementation of the appropriate medical interventions.
    Vortioxetine: (Moderate) Patients receiving a diuretic during treatment with vortioxetine may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Clinically significant hyponatremia has been reported during therapy with vortioxetine. One case involving serum sodium levels lower than 110 mmol/l has occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of vortioxetine should be considered in patients who develop symptomatic hyponatremia.
    Warfarin: (Minor) Per the prescribing information for warfarin sodium, concomitant use of diuretics (carbonic anhydrase inhibitors, loop diuretics, osmotic diuretics, potassium-sparing diuretics, and thiazide diuretics) and warfarin may result in an increased or decreased PT/INR. Patients should be monitored for changes in the INR when either of these drugs is initiated or discontinued, or if the dosage is changed.
    Yohimbine: (Moderate) Yohimbine can increase blood pressure and therefore can antagonize the therapeutic action of antihypertensive agents. Use with particular caution in hypertensive patients with high or uncontrolled BP.
    Ziconotide: (Moderate) Patients taking diuretics with ziconotide may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, consideration of diuretic cessation is warranted in addition to ziconotide discontinuation.
    Ziprasidone: (Moderate) Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents. Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope.

    PREGNANCY AND LACTATION

    Pregnancy

    Amiloride is classified as pregnancy category B. There are no adequate and well-controlled studies in pregnant women. According to the manufacturer, the drug should be administered to pregnant women only when the potential benefits to the mother outweigh the potential risk to the fetus. In general, diuretics are contraindicated in pregnant women with mild edema that is unresponsive to supportive measures (elevation of the lower extremities and the use of support hose) and edema which is not associated with more severe disease. Diuretics do not prevent the development of toxemia of pregnancy.

    According to the manufacturer, a decision should be made whether to discontinue breast-feeding or to discontinue amiloride. It is not known whether amiloride is excreted in human milk ; however, the molecular weight of the drug is low enough for excretion into breast-milk to occur. Amiloride has not been evaluated by the American Academy of Pediatrics (AAP). Spironolactone is classified by the AAP as usually compatible with breast-feeding and may represent a reasonable alternative for some patients. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    Amiloride, like triamterene, inhibits the sodium-potassium ion exchange mechanism in the distal renal tubule. The drug appears to interfere directly with sodium reabsorption in the distal tubule by inhibiting sodium transport mechanisms. An electrical-potential difference across the membrane is created, which acts to block the passive distal tubular secretion of potassium. This action is the primary cause of amiloride's potassium-sparing effects. Increased urinary excretion of sodium, bicarbonate, calcium, and water lead to a slight diuresis. Amiloride, unlike spironolactone, is not an aldosterone antagonist. It also does not inhibit carbonic anhydrase activity.
     
    Amiloride is rarely used as the sole therapy to treat hypertension, but it does have mild hypotensive effects. Initially, diuretics lower blood pressure by decreasing cardiac output and reducing plasma and extracellular fluid volume. Cardiac output and the extracellular fluid volume eventually return to normal, but peripheral resistance is reduced, resulting in lower blood pressure. In general, diuretics worsen glucose tolerance, and exert detrimental effects on the lipid profile.

    PHARMACOKINETICS

    Amiloride is administered orally. The onset of diuresis is generally 2 hours after administration, with peak effects at 6—10 hours and a duration of action of 24 hours. The drug is 40% plasma protein-bound. The volume of distribution of amiloride suggests extensive extravascular distribution. It has been shown to cross the placenta and distribute into breast milk in animals, although it is not known if this also occurs in humans. Amiloride is not metabolized by the liver. Approximately 50% of a dose is excreted unchanged in the urine and another 40% excreted unchanged in the feces, possibly as unabsorbed drug or secondary to biliary elimination. The half-life is 6—9 hours in patients with normal renal function.

    Oral Route

    Approximately 50% of a dose of amiloride is absorbed after oral administration; peak amiloride plasma levels are obtained within 3—4 hours. Food can decrease the extent of absorption by 50%, but the rate of absorption is not altered.