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    Loop Diuretics

    BOXED WARNING

    Acid/base imbalance, electrolyte imbalance, hypocalcemia, hypochloremia, hypokalemia, hypomagnesemia, hyponatremia, metabolic alkalosis

    Bumetanide is a potent diuretic and can cause electrolyte imbalance. Patients should be carefully monitored; dosage adjustments may be necessary. Because of this, bumetanide is contraindicated in patients with severe electrolyte imbalance until the condition is improved or corrected. Significant hyponatremia, hypokalemia, hypocalcemia, hypochloremia, and/or hypomagnesemia should be corrected before administration. Loop diuretics may induce metabolic alkalosis associated with hypokalemia and hypochloremia; this acid/base imbalance is effectively treated with potassium chloride replacement.

    Anuria, dehydration, hypovolemia, oliguria, renal disease, renal failure, renal impairment

    Bumetanide can cause dehydration; the dehydration can be profound if bumetanide is given in excessive doses. Patients should be carefully monitored; dosage adjustments may be necessary. Because of this, bumetanide is contraindicated in any patient with anuria. Bumetanide should be used with caution in patients with severe renal disease such as severe renal impairment or renal failure. Bumetanide-induced hypovolemia can precipitate oliguria and azotemia in these patients. Although bumetanide can be used to induce diuresis in renal insufficiency, any marked increase in blood urea nitrogen or serum creatinine, or the development of oliguria during therapy of patients with progressive renal disease, is an indication for discontinuation of treatment with bumetanide. Renal failure may reduce drug clearance and warrant the use of higher doses with extended dosing intervals. Bumetanide may be less effective in patients with renal failure and higher doses may be required. Delayed excretion of bumetanide in patients with renal failure may increase the risk of toxicity (e.g., ototoxicity).

    DEA CLASS

    Rx

    DESCRIPTION

    Oral and parenteral loop diuretic related to furosemide with a diuretic potency is about 40 times greater; useful in patients unresponsive to other diuretics.

    COMMON BRAND NAMES

    Bumex

    HOW SUPPLIED

    Bumetanide Intramuscular Inj Sol: 0.25mg, 1mL
    Bumetanide Intravenous Inj Sol: 0.25mg, 1mL
    Bumetanide/Bumex Oral Tab: 0.5mg, 1mg, 2mg

    DOSAGE & INDICATIONS

    For the treatment of peripheral edema or edema associated with heart failure or nephrotic syndrome.
    Oral dosage
    Adults

    0.5 to 1 mg PO once daily, initially. May repeat a second or third dose every 4 to 5 hours as needed until the desired diuretic effect is attained. Usual dose: 0.5 to 2 mg/day. Max: 10 mg/day. Heart failure guidelines recommend adding a loop 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).

    Infants†, Children†, and Adolescents†

    0.015 to 0.1 mg/kg/dose PO every 6 to 24 hours; Max initial dose: 2 mg. 0.014 to 0.15 mg/kg/dose PO every 24 to 48 hours was safe and effective for long-term use (4 to 20 weeks) in a study of infants with congenital heart disease and heart failure. Although a maximum dose has not been specified, the maximum dose in adults is 10 mg/day PO.

    Neonates†

    0.01 to 0.05 mg/kg/dose PO every 24 to 48 hours. 0.012 to 0.03 mg/kg/dose PO every 24 to 48 hours was safe and effective for long-term use (2 to 40 weeks) in a study of infants with congenital heart disease and heart failure; 5 patients were younger than 1 month of age at therapy initiation.

    Intravenous or Intramuscular dosage
    Adults

    0.5 to 1 mg IV or IM once, initially. May repeat a second or third dose every 2 to 3 hours as needed until the desired diuretic effect is attained. Max: 10 mg/day. Heart failure guidelines recommend adding a loop 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).

    Infants†, Children†, and Adolescents†

    0.015 to 0.1 mg/kg/dose IV or IM every 6 to 24 hours; Max initial dose: 1 mg. A dose ranging study in 56 infants 6 months or younger assessed diuretic response after single doses of 0.005 to 0.1 mg/kg IV and determined that maximal diuretic response would be achieved with doses of 0.035 to 0.04 mg/kg/dose IV every 6 to 8 hours. Although a maximum dose has not been specified, the maximum dose in adults is 10 mg/day.

    Neonates†

    0.01 to 0.05 mg/kg/dose IV or IM every 24 to 48 hours. A dose ranging study in 56 neonates and infants (0 to 6 months of age) assessed diuretic response after single doses of 0.005 to 0.1 mg/kg IV and determined that maximal diuretic response would be achieved with doses of 0.035 to 0.04 mg/kg/dose IV every 6 to 8 hours; neonatal data were not reported separately. However, restricting the dosage interval to a minimum of 12 hours is recommended, especially in premature neonates, due to decreased clearance and risk of accumulation and resultant toxicity.

    Continuous Intravenous Infusion dosage†
    Adults

    1 mg IV bolus, then 0.5 to 2 mg/hour continuous IV infusion for heart failure-related edema. In acute diuretic resistance in patients with chronic renal insufficiency, 1 mg IV bolus then 0.912 mg/hour continuous IV infusion for 12 hours (concentration = 0.024 mg/mL) has been used successfully. Heart failure guidelines recommend adding a loop 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).

    Infants, Children, and Adolescents

    1 to 10 mcg/kg/hour continuous IV infusion. The expected dose of bumetanide is 1.25 to 10 mcg/kg/hour continuous IV infusion based on a standard furosemide infusion dose (0.05 to 0.4 mg/kg/hour), taking into account bumetanide IV is 40-fold more potent than furosemide IV. A mean dose of 5.7 +/- 2.2 mcg/kg/hour with a median duration of 3.3 days (range: 0.3 to 18.5 days) was reported in a single-center, retrospective chart review of 95 pediatric critical care patients (median age: 0.2 years, range: 0 to 15.7 years); 54% of patients reached negative fluid balance within 12 hours and 76% of patients reached negative fluid balance within 48 hours. A majority (60%) of patients also received concomitant intermittent diuretics. Another retrospective study (n = 40; mean age: 1.6 years) reported a mean initial and maximum dose of 30 and 50 mcg/kg/hour, respectively (range: 1 to 200 mcg/kg/hour); however, safety was not assessed.

    Neonates

    1 to 10 mcg/kg/hour continuous IV infusion. The expected dose of bumetanide is 1.25 to 10 mcg/kg/hour continuous IV infusion based on a standard furosemide infusion dose (0.05 to 0.4 mg/kg/hour), taking into account bumetanide IV is 40-fold more potent than furosemide IV. A mean dose of 5.7 +/- 2.2 mcg/kg/hour with a median duration of 3.3 days (range: 0.3 to 18.5 days) was reported in a single-center, retrospective chart review of 95 pediatric critical care patients (median age: 0.2 years, range: 0 to 15.7 years); 54% of patients reached negative fluid balance within 12 hours and 76% of patients reached negative fluid balance within 48 hours. A majority (60%) of patients also received concomitant intermittent diuretics. Another retrospective study (n = 40; mean age: 1.6 years) reported a mean initial and maximum dose of 30 and 50 mcg/kg/hour, respectively (range: 1 to 200 mcg/kg/hour); however, safety was not assessed.

    For the treatment of hypertension†.
    Oral dosage
    Adults

    Initially, 0.5—2 mg PO once daily. Multiple daily doses may be given at 4—5 hour intervals if the response is not adequate. Maximum dosage is 10 mg/day, given in 2 divided doses.

    Geriatric

    See adult dosage. Geriatric patients may be more sensitive to the effects of the usual adult dosage.

    For the acute treatment of hypercalcemia† associated with neoplastic disease in combination with intravenous saline.
    Intravenous dosage
    Adults

    Initially, 1—2 mg IV every 1—4 hours to maintain an urine output of 200—250 mL/hour. Saline administration should begin before the first dose of bumetanide is administered to avoid volume contraction which may limit calciuria.

    Geriatric

    See adult dosage. Geriatric patients may be more sensitive to the effects of the usual adult dosage.

    For the treatment of ascites†.
    Oral or Intravenous dosage
    Adults

    Loop diuretics, preferably in combination with spironolactone or amiloride, are used for the treatment of ascites. While most data was generated with furosemide, bumetanide would be expected to provide a similar response. Initially, bumetanide 1 mg PO or IV once daily, can be added to therapy with an aldosterone antagonist or a potassium-sparing diuretic. If necessary titrate upwards by doubling the dose of each agent to achieve a satisfactory diuretic response. Based on recommendations for furosemide, the maximum equivalent dose of bumetanide should not exceed 4 mg/day in the treatment of ascites. Doses up to 6 mg PO once daily have been used, however, during long-term administration.

    Geriatric

    See adult dosage. Geriatric patients may be more sensitive to the effects of the usual adult dosage.

    For the treatment of oliguria† associated with acute renal failure in premature neonates.
    Intravenous dosage
    Premature Neonates

    0.01 to 0.06 mg/kg/dose IV every 12 to 24 hours was used in a retrospective study of 35 premature neonates (gestational age 24 to 33 weeks, postnatal age 6 to 37 days). Mean urinary output increased from 0.6 +/- 0.6 mL/kg/hour to 3 +/- 2.1 mL/kg/hour within 24 to 48 hours of starting bumetanide. Transient increases in serum creatinine also occurred during bumetanide therapy compared to baseline (2.13 vs. 2.31 mg/dL); however, these elevations began to decline 24 to 48 hours after the last dose of bumetanide and had returned to normal 4 to 5 weeks after the last dose in those patients available for follow-up.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    10 mg/day PO, IV, or IM.

    Geriatric

    10 mg/day PO, IV, or IM.

    Adolescents

    Safety and efficacy have not been established; however, doses up to 0.1 mg/kg/dose PO, IV, or IM have been used off-label (Max adult dose: 10 mg/day).

    Children

    Safety and efficacy have not been established; however, doses up to 0.1 mg/kg/dose PO, IV, or IM have been used off-label (Max adult dose: 10 mg/day).

    Infants

    Safety and efficacy have not been established; however, doses up to 0.1 mg/kg/dose PO, IV, or IM have been used off-label.

    Neonates

    Safety and efficacy have not been established; however, doses up to 0.06 mg/kg/dose IV have been used off-label for oliguria.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; start at the lower end of the dosage range and titrate carefully to desired response. See specific dosage for the treatment of ascites. In general, use diuretics with caution in patients with hepatic disease because minor alterations of fluid and electrolyte balance may precipitate hepatic coma.

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available; higher doses with extended dosage intervals may be effective in patients with end-stage renal disease (ESRD). Bumetanide is contraindicated in patients with anuria.

    ADMINISTRATION

    For storage information, see the specific product information in the How Supplied section.

    Oral Administration

    May administer without regard to meals.

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
    Updates for coronavirus disease 2019 (COVID-19): The FDA is allowing bumetanide 0.25 mg/mL to be used beyond the labeled in-use time to help ensure access during COVID-related drug shortages. This period should be as short as possible, and for a maximum of 2 hours at room temperature or 4 hours when refrigerated. In-use time is defined as the maximum amount of time allowed to elapse between penetration of a closed-container system or after reconstitution of a lyophilized drug before patient administration.

    Intravenous Administration

    Dilution
    May be diluted in 5% Dextrose Injection, 0.9% Sodium Chloride Injection, or Lactated Ringer's Injection.[52305]
    ASHP Recommended Standard Concentrations for Adult Continuous Infusions: 0.25 mg/mL (undiluted).[64020]
    ASHP Recommended Standard Concentrations for Pediatric Continuous Infusions: 0.04 mg/mL or 0.25 mg/mL.
    Storage: Use diluted solutions within 24 hours.[52305]
     
    IV Push
    No dilution necessary.
    Inject slowly over 1 to 2 minutes.[52305]
     
    IV Infusion
    No dilution necessary.[52305]

    Intramuscular Administration

    No dilution necessary.
    Inject deeply into a large muscle (i.e., upper outer quadrant of the gluteus maximus or lateral part of the thigh).

    STORAGE

    Generic:
    - Avoid extreme temperatures
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Discard unused portion. Do not store for later use.
    - Protect from direct sunlight
    - Protect from light
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    - Store in a cool, dry place
    Bumex:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Sulfonamide hypersensitivity, thiazide diuretic hypersensitivity

    Bumetanide is contraindicated in patients with known bumetanide hypersensitivity. Because cross-sensitivity with furosemide has rarely been observed, bumetanide can be substituted for furosemide in patients allergic to furosemide. The risk of an allergic reaction after administration of a loop diuretic in a patient with sulfonamide hypersensitivity or thiazide diuretic hypersensitivity appears to be very low. Although bumetanide is a sulfonamide derivative, sulfonamide cross-sensitivity has been rarely documented. A case report, published in 1987, documents an anaphylactic reaction to IV furosemide in a patient who was subsequently skin-tested with furosemide, bumetanide, ethacrynic acid, chlorothiazide, and sulfamethoxazole-trimethoprim. A positive reaction was elicited to all except ethacrynic acid. This case documents hypersensitivity to both furosemide and bumetanide in a patient with sulfonamide hypersensitivity. Prior to this, neither the FDA nor the manufacturer of furosemide (Lasix) had received any reports of cross-sensitivity between furosemide and sulfonamide antibiotics. Bumetanide does not contain the N4-aromatic amine or the N1-substituent which are present in sulfonamide antibiotics. Non-arylamine sulfonamide derivatives, such as loop diuretics, have been proposed to have a lower risk of allergic reactions in patients with sulfonamide allergy, presumably due to lack of an arylamine group at the N4 position (a proposed structural site of action for sulfonamide allergy). One large retrospective cohort study has reported that in patients with the presence of an allergic reaction after exposure to a sulfonamide antibiotic, 9.9% had an allergic reaction after receiving a non-antibiotic sulfonamide derivative, while in patients who lacked an allergic reaction after sulfonamide antibiotic exposure, 1.6% had an allergic reaction after administration of a non-antibiotic sulfonamide derivative (adjusted odds ratio 2.8; 95% CI, 2.1—3.7). A causal relationship between sulfonamide hypersensitivity and allergic reactions with non-arylamine sulfonamide derivatives has not been definitively established and remains controversial. In general, patients with a documented sulfonamide allergy are considered to be predisposed for development of allergic drug reactions.

    Acid/base imbalance, electrolyte imbalance, hypocalcemia, hypochloremia, hypokalemia, hypomagnesemia, hyponatremia, metabolic alkalosis

    Bumetanide is a potent diuretic and can cause electrolyte imbalance. Patients should be carefully monitored; dosage adjustments may be necessary. Because of this, bumetanide is contraindicated in patients with severe electrolyte imbalance until the condition is improved or corrected. Significant hyponatremia, hypokalemia, hypocalcemia, hypochloremia, and/or hypomagnesemia should be corrected before administration. Loop diuretics may induce metabolic alkalosis associated with hypokalemia and hypochloremia; this acid/base imbalance is effectively treated with potassium chloride replacement.

    Hepatic disease, hepatic encephalopathy

    Bumetanide is contraindicated in patients in hepatic encephalopathy (hepatic coma) until the condition is improved or corrected. Bumetanide-induced fluctuations in serum electrolyte concentrations can occur rapidly and precipitate serious hepatic effects in susceptible patients, including hepatic encephalopathy and/or coma. Bumetanide should be used with caution in patients with significant hepatic disease such as cirrhosis with ascites.

    Diabetes mellitus, hyperglycemia

    Blood and/or urine glucose levels should be monitored closely in patients with diabetes mellitus receiving bumetanide because loop diuretics can impair glucose tolerance resulting in hyperglycemia.

    Anuria, dehydration, hypovolemia, oliguria, renal disease, renal failure, renal impairment

    Bumetanide can cause dehydration; the dehydration can be profound if bumetanide is given in excessive doses. Patients should be carefully monitored; dosage adjustments may be necessary. Because of this, bumetanide is contraindicated in any patient with anuria. Bumetanide should be used with caution in patients with severe renal disease such as severe renal impairment or renal failure. Bumetanide-induced hypovolemia can precipitate oliguria and azotemia in these patients. Although bumetanide can be used to induce diuresis in renal insufficiency, any marked increase in blood urea nitrogen or serum creatinine, or the development of oliguria during therapy of patients with progressive renal disease, is an indication for discontinuation of treatment with bumetanide. Renal failure may reduce drug clearance and warrant the use of higher doses with extended dosing intervals. Bumetanide may be less effective in patients with renal failure and higher doses may be required. Delayed excretion of bumetanide in patients with renal failure may increase the risk of toxicity (e.g., ototoxicity).

    Hypotension, orthostatic hypotension, sympathectomy, syncope

    Patients with pre-existing hypovolemia or hypotension should have their condition corrected before bumetanide is initiated. Orthostatic hypotension may occur during treatment with loop diuretics. Excessive hypotension can result in syncope. The antihypertensive effects of diuretics may be enhanced in patients predisposed for orthostatic hypotension, including the post-sympathectomy patient.

    Gout, hyperuricemia

    Since loop diuretics (e.g., bumetanide) can reduce the clearance of uric acid, patients with gout or hyperuricemia can have exacerbations of their disease.

    Diarrhea, heart failure, ventricular arrhythmias

    Patients with ventricular arrhythmias, heart failure, potassium-losing nephropathy, aldosterone excess, or diarrhea should be monitored closely since bumetanide-induced hypokalemia can exacerbate these conditions.

    Acute myocardial infarction

    Excessive diuresis with bumetanide should be avoided in patients with acute myocardial infarction due to the risk of precipitating shock.

    Hearing impairment, tinnitus

    High doses and accumulation of bumetanide may cause ototoxicity. Bumetanide should be used with caution in patients with hearing impairment or tinnitus. Adverse otic effects occur more frequently in patients who are also receiving other ototoxic agents or who have severe renal impairment.

    Pancreatitis

    Bumetanide has been reported to cause pancreatitis. It should be used with caution in patients with a history of pancreatitis.

    Pregnancy

    There are no adequate and well-controlled studies of bumetanide in pregnant women. A small investigational experience and marketing experience have not indicated any evidence of adverse effects on the fetus; however, these data do not rule out the possibility of harmful effects. Use bumetanide during pregnancy only if the potential benefit justifies the potential risk to the fetus. Bumetanide has been shown to be nonteratogenic, but it has a slight embryocidal effect in rats when given in doses of 3,400 times the maximum human therapeutic dose (MRHD) and in rabbits at doses of 3.4 times the MRHD. Moderate growth retardation and increased incidence of delayed ossification of sternebrae were observed in rats at oral doses of 100 mg/kg/day (3,400 times the MRHD); these adverse effects were not observed at doses of 30 mg/kg/day (1,000 times the MRHD).[28620]

    Breast-feeding

    It is not known whether bumetanide is excreted in human milk. Avoid breast-feeding during bumetanide therapy since it may be excreted in human milk.[28620] Potent diuretics such as bumetanide may suppress lactation as a result of intense diuresis. Of note, previous American Academy of Pediatrics (AAP) recommendations considered bendroflumethiazide, chlorthalidone, chlorothiazide, and hydrochlorothiazide to be usually compatible with breast-feeding.[27500]

    Children, infants, jaundice, neonates

    Safety and efficacy of bumetanide has not been established in neonates, infants, children and adolescents under age 18 years. In vitro studies using pooled sera from critically ill neonates have shown bumetanide to be a potent displacer of bilirubin. The administration of bumetanide could present a particular concern if given to critically ill or neonates with jaundice who are at risk for kernicterus.

    Geriatric

    Greater sensitivity to the hypotensive and diuretic effects of bumetanide is possible in geriatric patients. Monitor renal function and for acid/base, fluid and electrolyte imbalances. According to the Beers Criteria, diuretics are considered potentially inappropriate medications (PIMs) in geriatric patients and should be used 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 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. In addition, diuretics may cause fluid and electrolyte imbalances and may precipitate or exacerbate urinary incontinence.

    ADVERSE REACTIONS

    Severe

    azotemia / Delayed / 10.6-10.6
    oliguria / Early / 0-1.0
    interstitial nephritis / Delayed / 0-1.0
    hearing loss / Delayed / 0-1.0
    toxic epidermal necrolysis / Delayed / 0-1.0
    Stevens-Johnson syndrome / Delayed / 0-1.0
    renal failure (unspecified) / Delayed / 0.5-0.5

    Moderate

    hyperuricemia / Delayed / 18.4-18.4
    hypochloremia / Delayed / 14.9-14.9
    hypokalemia / Delayed / 14.7-14.7
    orthostatic hypotension / Delayed / 1.0-10.0
    hypovolemia / Early / 1.0-10.0
    hyponatremia / Delayed / 9.2-9.2
    hyperglycemia / Delayed / 6.6-6.6
    hypophosphatemia / Delayed / 4.5-4.5
    hypocalcemia / Delayed / 2.4-2.4
    elevated hepatic enzymes / Delayed / 0-1.0
    leukopenia / Delayed / 0-1.0
    hypercholesterolemia / Delayed / 0-1.0
    hypertriglyceridemia / Delayed / 0-1.0
    hypotension / Rapid / 0.8-0.8
    glycosuria / Early / 0.7-0.7
    encephalopathy / Delayed / 0.6-0.6
    proteinuria / Delayed / 0.3-0.3
    thrombocytopenia / Delayed / 0.2-0.2
    impotence (erectile dysfunction) / Delayed / 0.1-0.1
    metabolic alkalosis / Delayed / Incidence not known
    hypomagnesemia / Delayed / Incidence not known
    dehydration / Delayed / Incidence not known

    Mild

    dizziness / Early / 1.1-1.1
    muscle cramps / Delayed / 1.1-1.1
    syncope / Early / 0-1.0
    tinnitus / Delayed / 0-1.0
    headache / Early / 0.6-0.6
    nausea / Early / 0.6-0.6
    pruritus / Rapid / 0.4-0.4
    weakness / Early / 0.2-0.2
    abdominal pain / Early / 0.2-0.2
    arthralgia / Delayed / 0.2-0.2
    vomiting / Early / 0.2-0.2
    musculoskeletal pain / Early / 0.2-0.2
    urticaria / Rapid / 0.2-0.2
    rash / Early / 0.2-0.2
    diaphoresis / Early / 0.1-0.1
    diarrhea / Early / 0.1-0.1
    vertigo / Early / 0.1-0.1
    fatigue / Early / 0.1-0.1
    xerostomia / Early / 0.1-0.1
    dyspepsia / Early / 0.1-0.1
    polyuria / Early / 10.0
    anorexia / Delayed / Incidence not known

    DRUG INTERACTIONS

    Acarbose: (Minor) Loop diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely.
    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 : (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 signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and codeine; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the 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; 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.
    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; Dichloralphenazone; Isometheptene: (Major) Isometheptene has sympathomimetic properties. Patients taking antihypertensive agents may need to have their therapy modified. Careful blood pressure monitoring is recommended.
    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 signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and hydrocodone; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
    Acetaminophen; Oxycodone: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and oxycodone; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
    Acetaminophen; Pentazocine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when loop 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.
    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.
    Albiglutide: (Minor) Loop diuretics, such as bumetanide, furosemide, and torsemide, may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between these drugs and all antidiabetic agents, including incretin mimetics. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if these drugs are initiated.
    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.
    Alendronate: (Moderate) When the intravenous formulation of alendronate is used for the treatment of hypercalcemia of malignancy, combination therapy with loop diuretics should be used with caution in order to avoid hypocalcemia. In patients with hypercalcemia of malignancy, the initial treatment typically includes the use of loop diuretics, in combination with saline hydration, however, diuretic therapy should not be employed prior to correction of hypovolemia and dehydration.
    Alendronate; Cholecalciferol: (Moderate) When the intravenous formulation of alendronate is used for the treatment of hypercalcemia of malignancy, combination therapy with loop diuretics should be used with caution in order to avoid hypocalcemia. In patients with hypercalcemia of malignancy, the initial treatment typically includes the use of loop diuretics, in combination with saline hydration, however, diuretic therapy should not be employed prior to correction of hypovolemia and dehydration.
    Alfentanil: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when a loop 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) Aliskiren can enhance the effects of loop-diuretics on blood pressure if given concomitantly. This additive effect may be desirable, but dosages must be adjusted accordingly. Patients with hyponatremia or hypovolemia may also develop reversible renal insufficiency. When aliskiren is administered in combination with furosemide, the AUC and Cmax of furosemide are reduced by approximately 30% and 50%, respectively; the pharmacokinetics of aliskiren are not affected. Patients should be monitored for loss of effect of furosemide when aliskiren is initiated. Blood pressure and electrolytes should be routinely monitored.
    Aliskiren; Amlodipine: (Moderate) Aliskiren can enhance the effects of loop-diuretics on blood pressure if given concomitantly. This additive effect may be desirable, but dosages must be adjusted accordingly. Patients with hyponatremia or hypovolemia may also develop reversible renal insufficiency. When aliskiren is administered in combination with furosemide, the AUC and Cmax of furosemide are reduced by approximately 30% and 50%, respectively; the pharmacokinetics of aliskiren are not affected. Patients should be monitored for loss of effect of furosemide when aliskiren is initiated. Blood pressure and electrolytes should be routinely monitored.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Aliskiren can enhance the effects of loop-diuretics on blood pressure if given concomitantly. This additive effect may be desirable, but dosages must be adjusted accordingly. Patients with hyponatremia or hypovolemia may also develop reversible renal insufficiency. When aliskiren is administered in combination with furosemide, the AUC and Cmax of furosemide are reduced by approximately 30% and 50%, respectively; the pharmacokinetics of aliskiren are not affected. Patients should be monitored for loss of effect of furosemide when aliskiren is initiated. Blood pressure and electrolytes should be routinely monitored. (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
    Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Aliskiren can enhance the effects of loop-diuretics on blood pressure if given concomitantly. This additive effect may be desirable, but dosages must be adjusted accordingly. Patients with hyponatremia or hypovolemia may also develop reversible renal insufficiency. When aliskiren is administered in combination with furosemide, the AUC and Cmax of furosemide are reduced by approximately 30% and 50%, respectively; the pharmacokinetics of aliskiren are not affected. Patients should be monitored for loss of effect of furosemide when aliskiren is initiated. Blood pressure and electrolytes should be routinely monitored. (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
    Aliskiren; Valsartan: (Moderate) Aliskiren can enhance the effects of loop-diuretics on blood pressure if given concomitantly. This additive effect may be desirable, but dosages must be adjusted accordingly. Patients with hyponatremia or hypovolemia may also develop reversible renal insufficiency. When aliskiren is administered in combination with furosemide, the AUC and Cmax of furosemide are reduced by approximately 30% and 50%, respectively; the pharmacokinetics of aliskiren are not affected. Patients should be monitored for loss of effect of furosemide when aliskiren is initiated. Blood pressure and electrolytes should be routinely monitored. (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative.
    Alogliptin: (Minor) Bumetanide may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between bumetanide and all antidiabetic agents, including alogliptin. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if this drug is initiated.
    Alogliptin; Metformin: (Minor) Bumetanide has been associated with hyperglycemia, possibly due to potassium depletion, and, glycosuria has been reported. Because of this, a potential pharmacodynamic interaction exists between bumetanide and all antidiabetic agents. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely. (Minor) Bumetanide may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between bumetanide and all antidiabetic agents, including alogliptin. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if this drug is initiated.
    Alogliptin; Pioglitazone: (Minor) Bumetanide has been associated with hyperglycemia, possibly due to potassium depletion, and, glycosuria has been reported. Because of this, a potential pharmacodynamic interaction exists between bumetanide and all antidiabetic agents. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely. (Minor) Bumetanide may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between bumetanide and all antidiabetic agents, including alogliptin. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if this drug is initiated.
    Alpha-glucosidase Inhibitors: (Minor) Loop diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely.
    Alprostadil: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as loop 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) Monitor potassium concentration before and during concomitant laxative, such as magnesium hydroxide, and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary.
    Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Moderate) Monitor potassium concentration before and during concomitant laxative, such as magnesium hydroxide, and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary.
    Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
    Aminoglycosides: (Moderate) The risk of ototoxicity or nephrotoxicity secondary to aminoglycosides may be increased by the addition of concomitant therapies with similar side effects, including loop diuretics. If loop diuretics and aminoglycosides are used together, it would be prudent to monitor renal function parameters, serum electrolytes, and serum aminoglycoside concentrations during therapy. Audiologic monitoring may be advisable during high dose therapy or therapy of long duration, when hearing loss is suspected, or in selected risk groups (e.g., neonates).
    Amiodarone: (Major) Monitor serum electrolytes if coadministration of bumetanide and amiodarone is necessary. Bumetanide therapy may cause electrolyte abnormalities (i.e., hypokalemia, hypomagnesemia) which may exaggerate the degree of QTc prolongation and increase the potential for torsade de pointes.
    Amlodipine; Benazepril: (Major) Discontinue the loop diuretic prior to starting benazepril, if possible, or start benazepril at the lower dose of 5 mg/day. Monitor blood pressure and renal function during concomitant use, particularly when doses are increased. Concomitant use may increase the risk for hypotension or renal failure.
    Amlodipine; Celecoxib: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. 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.
    Amlodipine; Olmesartan: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative.
    Amlodipine; Valsartan: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative.
    Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative. (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
    Amobarbital: (Moderate) Concurrent use of amobarbital with antihypertensive agents may lead to hypotension. Monitor for decreases in blood pressure during times of coadministration.
    Amoxicillin; Clarithromycin; Omeprazole: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and loop diuretic use due to risk for hypomagnesemia.
    Amphetamine: (Minor) Amphetamine and Dextroamphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as loop diuretics. Close monitoring of blood pressure is advised.
    Amphetamine; Dextroamphetamine Salts: (Minor) Amphetamine and Dextroamphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as loop diuretics. Close monitoring of blood pressure is advised.
    Amphetamine; Dextroamphetamine: (Minor) Amphetamine and Dextroamphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as loop diuretics. Close monitoring of blood pressure is advised.
    Amphotericin B cholesteryl sulfate complex (ABCD): (Moderate) Amphotericin B-induced hypokalemia can result in interactions with other drugs. Concurrent use of amphotericin B with loop diuretics can cause additive hypokalemia or hypomagnesemia due to renal potassium and magnesium wasting. It is prudent to monitor renal function parameters and serum electrolyte concentrations during co-therapy with loop diuretics and drugs which induce hypokalemia.
    Amphotericin B lipid complex (ABLC): (Moderate) Amphotericin B-induced hypokalemia can result in interactions with other drugs. Concurrent use of amphotericin B with loop diuretics can cause additive hypokalemia or hypomagnesemia due to renal potassium and magnesium wasting. It is prudent to monitor renal function parameters and serum electrolyte concentrations during co-therapy with loop diuretics and drugs which induce hypokalemia.
    Amphotericin B liposomal (LAmB): (Moderate) Amphotericin B-induced hypokalemia can result in interactions with other drugs. Concurrent use of amphotericin B with loop diuretics can cause additive hypokalemia or hypomagnesemia due to renal potassium and magnesium wasting. It is prudent to monitor renal function parameters and serum electrolyte concentrations during co-therapy with loop diuretics and drugs which induce hypokalemia.
    Amphotericin B: (Moderate) Amphotericin B-induced hypokalemia can result in interactions with other drugs. Concurrent use of amphotericin B with loop diuretics can cause additive hypokalemia or hypomagnesemia due to renal potassium and magnesium wasting. It is prudent to monitor renal function parameters and serum electrolyte concentrations during co-therapy with loop diuretics and drugs which induce hypokalemia.
    Amyl Nitrite: (Moderate) Monitor blood pressure during concomitant loop diuretic and nitrate use due to risk for additive hypotension; dosage adjustments may be necessary.
    Angiotensin II receptor antagonists: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative.
    Apomorphine: (Moderate) Use of loop 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 concomitantly with loop diuretics, as these can cause electrolyte abnormalities, which can increase the risk of QT prolongation.
    Articaine; Epinephrine: (Moderate) Monitor blood pressure, heart rate, and serum potassium during concomitant epinephrine and loop diuretic use. Loop diuretics may antagonize the pressor effects and potentiate the arrhythmogenic and hypokalemic effects of epinephrine.
    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; Butalbital; Caffeine; Codeine: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and codeine; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
    Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and codeine; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
    Aspirin, ASA; Omeprazole: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and loop diuretic use due to risk for hypomagnesemia.
    Aspirin, ASA; Oxycodone: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and oxycodone; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
    Atenolol; Chlorthalidone: (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
    Atracurium: (Moderate) Concomitant use of neuromuscular blockers and loop diuretics may prolong neuromuscular blockade, possibly due to hypokalemia or alterations in potassium concentrations across the end-plate membrane.
    Azelastine; Fluticasone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
    Azilsartan: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative.
    Azilsartan; Chlorthalidone: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative. (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
    Bacitracin: (Minor) Additive nephrotoxicity may occur with concurrent use of systemic bacitracin and other nephrotoxic agents. When possible, avoid concomitant administration of systemic bacitracin and other nephrotoxic drugs such as loop diuretics. Topical administration of any preparation containing bacitracin, especially when applied to large surface areas, also should not be given with other drugs that have a nephrotoxic potential. (Minor) Additive nephrotoxicity may occur with concurrent use of these medicines. When possible, avoid concomitant administration of systemic bacitracin and loop diuretics. Use of topically administrated preparations containing bacitracin, especially when applied to large surface areas, may have additive nephrotoxic potential with loop diuretics.
    Bacitracin; Hydrocortisone; Neomycin; Polymyxin B: (Minor) Additive nephrotoxicity may occur with concurrent use of systemic bacitracin and other nephrotoxic agents. When possible, avoid concomitant administration of systemic bacitracin and other nephrotoxic drugs such as loop diuretics. Topical administration of any preparation containing bacitracin, especially when applied to large surface areas, also should not be given with other drugs that have a nephrotoxic potential.
    Bacitracin; Polymyxin B: (Minor) Additive nephrotoxicity may occur with concurrent use of systemic bacitracin and other nephrotoxic agents. When possible, avoid concomitant administration of systemic bacitracin and other nephrotoxic drugs such as loop diuretics. Topical administration of any preparation containing bacitracin, especially when applied to large surface areas, also should not be given with other drugs that have a nephrotoxic potential.
    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: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
    Belladonna; Opium: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when loop diuretics are 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) Discontinue the loop diuretic prior to starting benazepril, if possible, or start benazepril at the lower dose of 5 mg/day. Monitor blood pressure and renal function during concomitant use, particularly when doses are increased. Concomitant use may increase the risk for hypotension or renal failure.
    Benazepril; Hydrochlorothiazide, HCTZ: (Major) Discontinue the loop diuretic prior to starting benazepril, if possible, or start benazepril at the lower dose of 5 mg/day. Monitor blood pressure and renal function during concomitant use, particularly when doses are increased. Concomitant use may increase the risk for hypotension or renal failure. (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
    Bendroflumethiazide; Nadolol: (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
    Benzhydrocodone; Acetaminophen: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when loop diuretics are administered with benzhydrocodone. 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.
    Benzphetamine: (Minor) Benzphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as loop diuretics. Close monitoring of blood pressure is advised.
    Beta-agonists: (Moderate) Use beta-agonists and loop diuretics with caution due to risk for ECG changes and/or hypokalemia. The ECG changes and/or hypokalemia that may result from administration of loop diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded.
    Betamethasone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
    Bisacodyl: (Moderate) Loop diuretics may increase the risk of hypokalemia especially in patients receiving prolonged therapy with laxatives. Monitor serum potassium levels to determine the need for potassium supplementation and/or alteration in drug therapy.
    Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
    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; 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.
    Brompheniramine; 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; 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.
    Brompheniramine; Pseudoephedrine; Dextromethorphan: (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: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
    Budesonide; Formoterol: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
    Budesonide; Glycopyrrolate; Formoterol: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
    Bupivacaine; Epinephrine: (Moderate) Monitor blood pressure, heart rate, and serum potassium during concomitant epinephrine and loop diuretic use. Loop diuretics may antagonize the pressor effects and potentiate the arrhythmogenic and hypokalemic effects of epinephrine.
    Bupivacaine; Meloxicam: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. 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.
    Buprenorphine: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and buprenorphine; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
    Buprenorphine; Naloxone: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and buprenorphine; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
    Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and codeine; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
    Cabergoline: (Moderate) Cabergoline should be used cautiously with antihypertensive agents, including loop diuretics. Cabergoline has been associated with hypotension. Initial doses of cabergoline higher than 1 mg may produce orthostatic hypotension. It may be advisable to monitor blood pressure.
    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. In addition, loop diuretics may increase the risk of hypokalemia especially in patients receiving prolonged therapy with laxatives. Monitor serum potassium levels to determine the need for potassium supplementation and/or alteration in drug therapy.
    Canagliflozin: (Major) Assess and correct volume status before initiating canagliflozin in persons receiving concomitant loop diuretics. Monitor for signs and symptoms of volume depletion and loss of glycemic control after initiating therapy due to increased risk for volume depletion or hypotension and loss of blood glucose control. Persons receiving loop diuretics may be at increased risk for volume depletion or hypotension with concomitant canagliflozin therapy. Loop diuretics tend to produce hyperglycemia and may lead to loss of glycemic control.
    Canagliflozin; Metformin: (Major) Assess and correct volume status before initiating canagliflozin in persons receiving concomitant loop diuretics. Monitor for signs and symptoms of volume depletion and loss of glycemic control after initiating therapy due to increased risk for volume depletion or hypotension and loss of blood glucose control. Persons receiving loop diuretics may be at increased risk for volume depletion or hypotension with concomitant canagliflozin therapy. Loop diuretics tend to produce hyperglycemia and may lead to loss of glycemic control. (Minor) Bumetanide has been associated with hyperglycemia, possibly due to potassium depletion, and, glycosuria has been reported. Because of this, a potential pharmacodynamic interaction exists between bumetanide and all antidiabetic agents. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely.
    Candesartan: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative.
    Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative. (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
    Capreomycin: (Moderate) The risk of ototoxicity or nephrotoxicity secondary to capreomycin may be increased by the addition of concomitant therapies with similar side effects, including loop diuretics. Ototoxicity from furosemide or other loop diuretics, while uncommon, can be a transient or permanent side effect of significance. Ototoxicity is best documented with the loop diuretics ethacrynic acid and furosemide, but may also occur with either bumetanide or torsemide. The exact mechanism by which furosemide or other loop diuretics produce ototoxicity is unknown. Usually, reports indicate that furosemide ototoxicity is associated with rapid injection, severe renal impairment, higher than recommended dosages or infusion rates, or concomitant therapy with aminoglycoside antibiotics, ethacrynic acid, or other ototoxic drugs. If loop diuretics and capreomycin are used together, it would be prudent to monitor renal function parameters, serum electrolytes, and serum aminoglycoside concentrations during therapy. Audiologic monitoring may be advisable during high dose therapy or therapy of long duration, when hearing loss is suspected, or in selected risk groups (e.g., neonates).
    Captopril: (Major) Discontinue the loop diuretic prior to starting captopril, if possible, or start captopril at the lower dose of 6.25 or 12.5 mg/day. Monitor blood pressure and renal function during concomitant use, particularly when doses are increased. Concomitant use may increase the risk for hypotension or renal failure.
    Captopril; Hydrochlorothiazide, HCTZ: (Major) Discontinue the loop diuretic prior to starting captopril, if possible, or start captopril at the lower dose of 6.25 or 12.5 mg/day. Monitor blood pressure and renal function during concomitant use, particularly when doses are increased. Concomitant use may increase the risk for hypotension or renal failure. (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
    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) Monitor blood pressure during concomitant levodopa and loop diuretic use due to risk for additive hypotension; a loop diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
    Carbidopa; Levodopa; Entacapone: (Moderate) Monitor blood pressure during concomitant levodopa and loop diuretic use due to risk for additive hypotension; a loop diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
    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; 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.
    Cardiac glycosides: (Moderate) Monitor serum magnesium and potassium during concomitant cardiac glycoside and loop diuretic use. Potassium-depleting diuretics are a major contributing factor to digoxin toxicity.
    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.
    Castor Oil: (Moderate) Loop diuretics may increase the risk of hypokalemia especially in patients receiving prolonged therapy with laxatives. Monitor serum potassium levels to determine the need for potassium supplementation and/or alteration in drug therapy.
    Cefaclor: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
    Cefadroxil: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
    Cefazolin: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
    Cefdinir: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
    Cefditoren: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
    Cefepime: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
    Cefiderocol: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
    Cefixime: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
    Cefotaxime: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
    Cefotetan: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
    Cefoxitin: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
    Cefpodoxime: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
    Cefprozil: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
    Ceftaroline: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
    Ceftazidime: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
    Ceftazidime; Avibactam: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
    Ceftibuten: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
    Ceftizoxime: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
    Ceftolozane; Tazobactam: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
    Ceftriaxone: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
    Cefuroxime: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
    Celecoxib: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. 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.
    Celecoxib; Tramadol: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. 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. (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and tramadol; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
    Cephalexin: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
    Cephalosporins: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
    Cephalothin: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
    Cephradine: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
    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.
    Chloroprocaine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Chlorothiazide: (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
    Chlorpheniramine; Codeine: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and codeine; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the 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; 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.
    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; Hydrocodone: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and hydrocodone; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
    Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. 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. (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.
    Chlorthalidone: (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
    Chlorthalidone; Clonidine: (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
    Ciclesonide: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
    Cidofovir: (Contraindicated) 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.
    Cisapride: (Major) Cisapride should be used with great caution in patients receiving potassium-wasting diuretic therapies, such as loop diuretics. Drugs that are associated with depletion of electrolytes may cause cisapride-induced cardiac arrhythmias.
    Cisatracurium: (Moderate) Concomitant use of neuromuscular blockers and loop diuretics may prolong neuromuscular blockade, possibly due to hypokalemia or alterations in potassium concentrations across the end-plate membrane.
    Cisplatin: (Major) Avoid coadministration of bumetanide and cisplatin due to the risk of additive ototoxicity and nephrotoxicity. Both drugs can cause ototoxicity and nephrotoxicity; there has been no experience with the concurrent use of bumetanide and other nephrotoxic agents.
    Citalopram: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and citalopram use; consider discontinuing citalopram if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
    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 signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and codeine; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
    Codeine; Guaifenesin: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and codeine; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
    Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and codeine; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the 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.
    Codeine; Phenylephrine; Promethazine: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and codeine; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the 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 signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and codeine; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
    Co-Enzyme Q10, Ubiquinone: (Moderate) Monitor blood pressure during concomitant co-enzyme Q10 (ubiquinone) and loop diuretic use. Concomitant use may result in additive hypotension.
    Corticosteroids: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
    Cortisone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
    Cosyntropin: (Moderate) Use cosyntropin cautiously in patients receiving diuretics. Cosyntropin may accentuate the electrolyte loss associated with diuretic therapy.
    Dapagliflozin: (Moderate) Loop diuretics can decrease the hypoglycemic effects of antidiabetic agents by producing an increase in blood glucose concentrations. Patients receiving dapagliflozin should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary.
    Dapagliflozin; Metformin: (Moderate) Loop diuretics can decrease the hypoglycemic effects of antidiabetic agents by producing an increase in blood glucose concentrations. Patients receiving dapagliflozin should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. (Minor) Bumetanide has been associated with hyperglycemia, possibly due to potassium depletion, and, glycosuria has been reported. Because of this, a potential pharmacodynamic interaction exists between bumetanide and all antidiabetic agents. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely.
    Dapagliflozin; Saxagliptin: (Moderate) Loop diuretics can decrease the hypoglycemic effects of antidiabetic agents by producing an increase in blood glucose concentrations. Patients receiving dapagliflozin should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. (Minor) Bumetanide has been associated with hyperglycemia, possibly due to potassium depletion, and, glycosuria has been reported. Because of this, a potential pharmacodynamic interaction exists between bumetanide and all antidiabetic agents. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely.
    Darifenacin: (Minor) Diuretics can increase urinary frequency, which may aggravate bladder symptoms.
    Deflazacort: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
    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.
    Desmopressin: (Contraindicated) Desmopressin is contraindicated with concomitant loop diuretic use due to an increased risk of hyponatremia.
    Desvenlafaxine: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and serotonin norepinephrine reuptake inhibitor (SNRI) use; consider discontinuing the SNRI if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
    Dexamethasone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
    Dexbrompheniramine; 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.
    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.
    Dexlansoprazole: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with loop diuretics (furosemide, bumetanide, torsemide, and ethacrynic acid). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Dextroamphetamine: (Minor) Amphetamine and Dextroamphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as loop 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: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Diazoxide: (Moderate) Additive hypotensive effects can occur with the concomitant administration of diazoxide with loop diuretics. 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 bumetanide together with caution. Dichlorphenamide increases potassium excretion and can cause hypokalemia and should be used cautiously with other drugs that may cause hypokalemia including bumetanide. Measure potassium concentrations at baseline and periodically during dichlorphenamide treatment. If hypokalemia occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy.
    Diclofenac: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. 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.
    Diclofenac; Misoprostol: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. 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.
    Diethylpropion: (Major) Diethylpropion has vasopressor effects and may limit the benefit of loop diuretics. Although leading drug interaction texts differ in the potential for an interaction between diethylpropion and this group of antihypertensive agents, these effects are likely to be clinically significant and have been described in hypertensive patients on these medications.
    Diflunisal: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. 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.
    Digitoxin: (Moderate) Monitor serum magnesium and potassium during concomitant cardiac glycoside and loop diuretic use. Potassium-depleting diuretics are a major contributing factor to digoxin toxicity.
    Digoxin: (Moderate) Monitor serum magnesium and potassium during concomitant cardiac glycoside and loop diuretic use. Potassium-depleting diuretics are a major contributing factor to digoxin toxicity.
    Diphenhydramine; Ibuprofen: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. 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.
    Diphenhydramine; Naproxen: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. 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.
    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) Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs such as loop diuretics increasing the potential for dofetilide-induced torsade de pointes. Potassium levels should be within the normal range prior and during administration of dofetilide.
    Dolasetron: (Moderate) Caution is advisable during concurrent use of dolasetron and loop diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with dolasetron.
    Doxacurium: (Moderate) Concomitant use of neuromuscular blockers and loop diuretics may prolong neuromuscular blockade, possibly due to hypokalemia or alterations in potassium concentrations across the end-plate membrane.
    Droperidol: (Moderate) Caution is advised when using droperidol in combination with loop diuretics which may lead to electrolyte abnormalities, especially hypokalemia or hypomagnesemia, as such abnormalities may increase the risk for QT prolongation or cardiac arrhythmias.
    Dulaglutide: (Minor) Loop diuretics, such as bumetanide, furosemide, and torsemide, may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between these drugs and all antidiabetic agents, including incretin mimetics. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if these drugs are initiated.
    Duloxetine: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and serotonin norepinephrine reuptake inhibitor (SNRI) use; consider discontinuing the SNRI if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
    Empagliflozin: (Moderate) When empagliflozin is initiated in patients already receiving loop 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, volume status should be assessed and corrected. Monitor for signs and symptoms after initiating therapy. Loop diuretics can decrease the hypoglycemic effects of antidiabetic agents by producing an increase in blood glucose concentrations. Patients receiving empagliflozin should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary.
    Empagliflozin; Linagliptin: (Moderate) When empagliflozin is initiated in patients already receiving loop 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, volume status should be assessed and corrected. Monitor for signs and symptoms after initiating therapy. Loop diuretics can decrease the hypoglycemic effects of antidiabetic agents by producing an increase in blood glucose concentrations. Patients receiving empagliflozin should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. (Minor) Loop diurectics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between these drugs and all antidiabetic agents, such as linagliptin. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if these drugs are initiated.
    Empagliflozin; Linagliptin; Metformin: (Moderate) When empagliflozin is initiated in patients already receiving loop 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, volume status should be assessed and corrected. Monitor for signs and symptoms after initiating therapy. Loop diuretics can decrease the hypoglycemic effects of antidiabetic agents by producing an increase in blood glucose concentrations. Patients receiving empagliflozin should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. (Minor) Bumetanide has been associated with hyperglycemia, possibly due to potassium depletion, and, glycosuria has been reported. Because of this, a potential pharmacodynamic interaction exists between bumetanide and all antidiabetic agents. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely. (Minor) Loop diurectics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between these drugs and all antidiabetic agents, such as linagliptin. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if these drugs are initiated.
    Empagliflozin; Metformin: (Moderate) When empagliflozin is initiated in patients already receiving loop 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, volume status should be assessed and corrected. Monitor for signs and symptoms after initiating therapy. Loop diuretics can decrease the hypoglycemic effects of antidiabetic agents by producing an increase in blood glucose concentrations. Patients receiving empagliflozin should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. (Minor) Bumetanide has been associated with hyperglycemia, possibly due to potassium depletion, and, glycosuria has been reported. Because of this, a potential pharmacodynamic interaction exists between bumetanide and all antidiabetic agents. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely.
    Enalapril, Enalaprilat: (Major) Discontinue the loop diuretic prior to starting enalapril, if possible, or start enalapril at the lower dose of 2.5 mg/day. Monitor blood pressure and renal function during concomitant use, particularly when doses are increased. Concomitant use may increase the risk for hypotension or renal failure.
    Enalapril; Felodipine: (Major) Discontinue the loop diuretic prior to starting enalapril, if possible, or start enalapril at the lower dose of 2.5 mg/day. Monitor blood pressure and renal function during concomitant use, particularly when doses are increased. Concomitant use may increase the risk for hypotension or renal failure.
    Enalapril; Hydrochlorothiazide, HCTZ: (Major) Discontinue the loop diuretic prior to starting enalapril, if possible, or start enalapril at the lower dose of 2.5 mg/day. Monitor blood pressure and renal function during concomitant use, particularly when doses are increased. Concomitant use may increase the risk for hypotension or renal failure. (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
    Ephedrine: (Major) The cardiovascular effects of sympathomimetics, such as ephedrine, may reduce the antihypertensive effects produced by loop diuretics. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved.
    Ephedrine; Guaifenesin: (Major) The cardiovascular effects of sympathomimetics, such as ephedrine, may reduce the antihypertensive effects produced by loop diuretics. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved.
    Epinephrine: (Moderate) Monitor blood pressure, heart rate, and serum potassium during concomitant epinephrine and loop diuretic use. Loop diuretics may antagonize the pressor effects and potentiate the arrhythmogenic and hypokalemic effects of epinephrine.
    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: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative.
    Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative. (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
    Ertugliflozin; Metformin: (Minor) Bumetanide has been associated with hyperglycemia, possibly due to potassium depletion, and, glycosuria has been reported. Because of this, a potential pharmacodynamic interaction exists between bumetanide and all antidiabetic agents. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely.
    Ertugliflozin; Sitagliptin: (Minor) Bumetanide has been associated with hyperglycemia, possibly due to potassium depletion, and, glycosuria has been reported. Because of this, a potential pharmacodynamic interaction exists between bumetanide and all antidiabetic agents. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely.
    Escitalopram: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and escitalopram use; consider discontinuing escitalopram if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
    Esomeprazole: (Moderate) Monitor magnesium concentration before and periodically during concomitant esomeprazole and loop diuretic use due to risk for hypomagnesemia.
    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.
    Etodolac: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. 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.
    Etomidate: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Exenatide: (Minor) Loop diuretics, such as bumetanide, furosemide, and torsemide, may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between these drugs and all antidiabetic agents, including incretin mimetics. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if these drugs are initiated.
    Fenoprofen: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. 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.
    Fentanyl: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and fentanyl; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the 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) Monitor blood pressure during concomitant fish oil and loop diuretic use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
    Fludrocortisone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
    Flunisolide: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
    Fluoxetine: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and fluoxetine use; consider discontinuing fluoxetine if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
    Flurbiprofen: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. 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.
    Fluticasone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
    Fluticasone; Salmeterol: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
    Fluticasone; Umeclidinium; Vilanterol: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
    Fluticasone; Vilanterol: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
    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: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
    Foscarnet: (Moderate) Avoid concurrent use of loop diuretics with foscarnet. Coadministration may impair the renal tubular secretion of foscarnet, thereby increasing the possibility for toxicity. When use of a diuretic is indicated in patients being treated with foscarnet, consider a thiazide diuretic.
    Fosinopril: (Major) Discontinue the loop diuretic prior to starting fosinopril, if possible, or start fosinopril at a lower dose. Monitor blood pressure and renal function during concomitant use, particularly when doses are increased. Concomitant use may increase the risk for hypotension or renal failure.
    Fosinopril; Hydrochlorothiazide, HCTZ: (Major) Discontinue the loop diuretic prior to starting fosinopril, if possible, or start fosinopril at a lower dose. Monitor blood pressure and renal function during concomitant use, particularly when doses are increased. Concomitant use may increase the risk for hypotension or renal failure. (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
    General anesthetics: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Ginseng, Panax ginseng: (Major) Ginseng may decrease the effectiveness of loop diuretics. One case report described a temporal relationship between the use of ginseng and resistance to furosemide therapy, resulting in edema, hypertension, and hospitalization on 2 separate occasions. Other nutritional products were taken concurrently by the patient were not specified in the report. A mechanism of action or causal relationship has not been definitively established.
    Glimepiride; Rosiglitazone: (Minor) Bumetanide has been associated with hyperglycemia, possibly due to potassium depletion, and, glycosuria has been reported. Because of this, a potential pharmacodynamic interaction exists between bumetanide and all antidiabetic agents. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely.
    Glipizide; Metformin: (Minor) Bumetanide has been associated with hyperglycemia, possibly due to potassium depletion, and, glycosuria has been reported. Because of this, a potential pharmacodynamic interaction exists between bumetanide and all antidiabetic agents. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely.
    Glyburide; Metformin: (Minor) Bumetanide has been associated with hyperglycemia, possibly due to potassium depletion, and, glycosuria has been reported. Because of this, a potential pharmacodynamic interaction exists between bumetanide and all antidiabetic agents. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely.
    Granisetron: (Moderate) According to the manufacturer, caution is warranted when administering granisetron to patients with preexisting electrolyte abnormalities. Patients taking certain diuretics may develop an electrolyte abnormality that may lead to cardiac dysrhythmias and/or QT prolongation. Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs such as loop diuretics and thiazide diuretics, increasing the potential for cardiac arrhythmias.
    Guaifenesin; Hydrocodone: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and hydrocodone; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and hydrocodone; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the 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) Caution is advisable during concurrent use of haloperidol and loop diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with haloperidol. Concomitant use may also cause additive hypotension.
    Homatropine; Hydrocodone: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and hydrocodone; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
    Hydralazine; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
    Hydralazine; Isosorbide Dinitrate, ISDN: (Moderate) Monitor blood pressure during concomitant loop diuretic and nitrate use due to risk for additive hypotension; dosage adjustments may be necessary.
    Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
    Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
    Hydrochlorothiazide, HCTZ; Moexipril: (Major) Discontinue the loop diuretic prior to starting moexipril, if possible, or start moexipril at the lower dose of 3.75 mg/day. Monitor blood pressure and renal function during concomitant use, particularly when doses are increased. Concomitant use may increase the risk for hypotension or renal failure. (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
    Hydrocodone: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and hydrocodone; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
    Hydrocodone; Ibuprofen: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. 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. (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and hydrocodone; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
    Hydrocodone; Pseudoephedrine: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and hydrocodone; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the 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: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
    Hydromorphone: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when loop diuretics are 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.
    Ibandronate: (Moderate) When the intravenous formulation of ibandronate is used for the treatment of hypercalcemia of malignancy, combination therapy with loop diuretics should be used with caution in order to avoid hypocalcemia. In patients with hypercalcemia of malignancy, the initial treatment typically includes the use of loop diuretics, in combination with saline hydration, however, diuretic therapy should not be employed prior to correction of hypovolemia and dehydration.
    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: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. 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.
    Ibuprofen; Famotidine: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. 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.
    Ibuprofen; Oxycodone: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. 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. (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and oxycodone; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
    Ibuprofen; Pseudoephedrine: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. 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. (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) Further reductions in blood pressure may occur when inhaled iloprost is administered to patients receiving other antihypertensive agents.
    Incretin Mimetics: (Minor) Loop diuretics, such as bumetanide, furosemide, and torsemide, may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between these drugs and all antidiabetic agents, including incretin mimetics. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if these drugs are initiated.
    Indomethacin: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. 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.
    Inotersen: (Moderate) Use caution with concomitant use of inotersen and diuretics due to the risk of glomerulonephritis and nephrotoxicity.
    Insulin Degludec; Liraglutide: (Minor) Loop diuretics, such as bumetanide, furosemide, and torsemide, may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between these drugs and all antidiabetic agents, including incretin mimetics. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if these drugs are initiated.
    Insulin Glargine; Lixisenatide: (Minor) Loop diuretics, such as bumetanide, furosemide, and torsemide, may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between these drugs and all antidiabetic agents, including incretin mimetics. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if these drugs are initiated.
    Insulins: (Minor) Monitor patients receiving insulin closely for worsening glycemic control when bumetanide, furosemide, and torsemide are instituted. Bumetanide, furosemide, and torsemide may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between these drugs and all antidiabetic agents.
    Intravenous Lipid Emulsions: (Moderate) Monitor blood pressure during concomitant fish oil and loop diuretic use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
    Irbesartan: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative.
    Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative. (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
    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) Monitor blood pressure during concomitant loop diuretic and nitrate use due to risk for additive hypotension; dosage adjustments may be necessary.
    Isosorbide Mononitrate: (Moderate) Monitor blood pressure during concomitant loop diuretic and nitrate use due to risk for additive hypotension; dosage adjustments may be necessary.
    Ketamine: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Ketoprofen: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. 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.
    Ketorolac: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. 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.
    Lactulose: (Moderate) Loop diuretics may increase the risk of hypokalemia especially in patients receiving prolonged therapy with laxatives. Monitor serum potassium levels to determine the need for potassium supplementation and/or alteration in drug therapy.
    Lansoprazole: (Moderate) Monitor magnesium concentration before and periodically during concomitant lansoprazole and loop diuretic use due to risk for hypomagnesemia.
    Lansoprazole; Amoxicillin; Clarithromycin: (Moderate) Monitor magnesium concentration before and periodically during concomitant lansoprazole and loop diuretic use due to risk for hypomagnesemia.
    Lansoprazole; Naproxen: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. 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. (Moderate) Monitor magnesium concentration before and periodically during concomitant lansoprazole and loop diuretic use due to risk for hypomagnesemia.
    Levodopa: (Moderate) Monitor blood pressure during concomitant levodopa and loop diuretic use due to risk for additive hypotension; a loop diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
    Levomilnacipran: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and serotonin norepinephrine reuptake inhibitor (SNRI) use; consider discontinuing the SNRI if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
    Levorphanol: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when loop diuretics are 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.
    Lidocaine; Epinephrine: (Moderate) Monitor blood pressure, heart rate, and serum potassium during concomitant epinephrine and loop diuretic use. Loop diuretics may antagonize the pressor effects and potentiate the arrhythmogenic and hypokalemic effects of epinephrine.
    Linagliptin: (Minor) Loop diurectics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between these drugs and all antidiabetic agents, such as linagliptin. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if these drugs are initiated.
    Linagliptin; Metformin: (Minor) Bumetanide has been associated with hyperglycemia, possibly due to potassium depletion, and, glycosuria has been reported. Because of this, a potential pharmacodynamic interaction exists between bumetanide and all antidiabetic agents. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely. (Minor) Loop diurectics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between these drugs and all antidiabetic agents, such as linagliptin. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if these drugs are initiated.
    Liraglutide: (Minor) Loop diuretics, such as bumetanide, furosemide, and torsemide, may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between these drugs and all antidiabetic agents, including incretin mimetics. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if these drugs are initiated.
    Lisdexamfetamine: (Minor) Lisdexamfetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as loop diuretics. Close monitoring of blood pressure is advised.
    Lisinopril: (Major) Discontinue the loop diuretic prior to starting lisinopril, if possible, or start lisinopril at the lower dose of 5 mg/day. Monitor blood pressure and renal function during concomitant use, particularly when doses are increased. Concomitant use may increase the risk for hypotension or renal failure.
    Lisinopril; Hydrochlorothiazide, HCTZ: (Major) Discontinue the loop diuretic prior to starting lisinopril, if possible, or start lisinopril at the lower dose of 5 mg/day. Monitor blood pressure and renal function during concomitant use, particularly when doses are increased. Concomitant use may increase the risk for hypotension or renal failure. (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
    Lithium: (Moderate) Monitor serum electrolyte and lithium concentrations during concomitant loop diuretic use; reduce the lithium dose based on serum lithium concentration and clinical response. Diuretic-induced sodium loss may reduce lithium clearance and increase lithium serum concentrations.
    Lixisenatide: (Minor) Loop diuretics, such as bumetanide, furosemide, and torsemide, may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between these drugs and all antidiabetic agents, including incretin mimetics. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if these drugs are initiated.
    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: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative.
    Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative. (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
    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.
    Lubiprostone: (Moderate) Loop diuretics may increase the risk of hypokalemia especially in patients receiving prolonged therapy with laxatives. Monitor serum potassium levels to determine the need for potassium supplementation and/or alteration in drug therapy.
    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) Monitor potassium concentration before and during concomitant laxative, such as magnesium citrate, and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary.
    Magnesium Hydroxide: (Moderate) Monitor potassium concentration before and during concomitant laxative, such as magnesium hydroxide, and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary.
    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.
    Meclofenamate Sodium: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. 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.
    Mefenamic Acid: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. 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.
    Meglitinides: (Minor) Loop diuretics have been associated with hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between loop diuretics and all antidiabetic agents. Monitor for a loss of diabetic control.
    Meloxicam: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. 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.
    Meperidine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when loop diuretics are 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 loop diuretics are 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.
    Metformin: (Minor) Bumetanide has been associated with hyperglycemia, possibly due to potassium depletion, and, glycosuria has been reported. Because of this, a potential pharmacodynamic interaction exists between bumetanide and all antidiabetic agents. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely.
    Metformin; Repaglinide: (Minor) Bumetanide has been associated with hyperglycemia, possibly due to potassium depletion, and, glycosuria has been reported. Because of this, a potential pharmacodynamic interaction exists between bumetanide and all antidiabetic agents. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely. (Minor) Loop diuretics have been associated with hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between loop diuretics and all antidiabetic agents. Monitor for a loss of diabetic control.
    Metformin; Rosiglitazone: (Minor) Bumetanide has been associated with hyperglycemia, possibly due to potassium depletion, and, glycosuria has been reported. Because of this, a potential pharmacodynamic interaction exists between bumetanide and all antidiabetic agents. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely.
    Metformin; Saxagliptin: (Minor) Bumetanide has been associated with hyperglycemia, possibly due to potassium depletion, and, glycosuria has been reported. Because of this, a potential pharmacodynamic interaction exists between bumetanide and all antidiabetic agents. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely.
    Metformin; Sitagliptin: (Minor) Bumetanide has been associated with hyperglycemia, possibly due to potassium depletion, and, glycosuria has been reported. Because of this, a potential pharmacodynamic interaction exists between bumetanide and all antidiabetic agents. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely.
    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.
    Methamphetamine: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as loop diuretics. Close monitoring of blood pressure is advised.
    Methazolamide: (Moderate) Loop diuretics may increase the risk of hypokalemia if used concurrently with methazolamide. Monitor serum potassium levels to determine the need for potassium supplementation and/or alteration in drug therapy. There may also be an additive diuretic or hyperuricemic effect.
    Methohexital: (Moderate) Concurrent use of methohexital and antihypertensive agents increases the risk of developing hypotension.
    Methyclothiazide: (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
    Methylcellulose: (Moderate) Loop diuretics may increase the risk of hypokalemia especially in patients receiving prolonged therapy with laxatives. Monitor serum potassium levels to determine the need for potassium supplementation and/or alteration in drug therapy.
    Methylphenidate Derivatives: (Moderate) Monitor blood pressure during concomitant loop diuretic and methylphenidate use; a loop diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
    Methylprednisolone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
    Metolazone: (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
    Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
    Miglitol: (Minor) Loop diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely.
    Milnacipran: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and serotonin norepinephrine reuptake inhibitor (SNRI) use; consider discontinuing the SNRI if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
    Milrinone: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
    Mineral Oil: (Moderate) Loop diuretics may increase the risk of hypokalemia especially in patients receiving prolonged therapy with laxatives. Monitor serum potassium levels to determine the need for potassium supplementation and/or alteration in drug therapy.
    Mirtazapine: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and mirtazapine use; consider discontinuing mirtazapine if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
    Mivacurium: (Moderate) Concomitant use of neuromuscular blockers and loop diuretics may prolong neuromuscular blockade, possibly due to hypokalemia or alterations in potassium concentrations across the end-plate membrane.
    Moexipril: (Major) Discontinue the loop diuretic prior to starting moexipril, if possible, or start moexipril at the lower dose of 3.75 mg/day. Monitor blood pressure and renal function during concomitant use, particularly when doses are increased. Concomitant use may increase the risk for hypotension or renal failure.
    Mometasone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
    Morphine: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and morphine; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
    Morphine; Naltrexone: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and morphine; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
    Nabumetone: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. 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.
    Naproxen: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. 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.
    Naproxen; Esomeprazole: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. 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. (Moderate) Monitor magnesium concentration before and periodically during concomitant esomeprazole and loop diuretic use due to risk for hypomagnesemia.
    Naproxen; Pseudoephedrine: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. 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. (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.
    Nateglinide: (Minor) Loop diuretics have been associated with hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between loop diuretics and all antidiabetic agents. Monitor for a loss of diabetic control.
    Nebivolol; Valsartan: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative.
    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.
    Neomycin; Polymyxin B; Bacitracin: (Minor) Additive nephrotoxicity may occur with concurrent use of systemic bacitracin and other nephrotoxic agents. When possible, avoid concomitant administration of systemic bacitracin and other nephrotoxic drugs such as loop diuretics. Topical administration of any preparation containing bacitracin, especially when applied to large surface areas, also should not be given with other drugs that have a nephrotoxic potential.
    Nesiritide, BNP: (Major) The potential for hypotension may be increased when coadministering nesiritide with antihypertensive agents.
    Neuromuscular blockers: (Moderate) Concomitant use of neuromuscular blockers and loop diuretics may prolong neuromuscular blockade, possibly due to hypokalemia or alterations in potassium concentrations across the end-plate membrane.
    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) Monitor blood pressure during concomitant loop diuretic and nitrate use due to risk for additive hypotension; dosage adjustments may be necessary.
    Nitroglycerin: (Moderate) Monitor blood pressure during concomitant loop diuretic and nitrate use due to risk for additive hypotension; 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.
    Non-Ionic Contrast Media: (Major) Do not use diuretics before non-ionic contrast media administration. Concomitant use of diuretics and non-ionic contrast media may increase the risk for acute kidney injury, including renal failure.
    Norepinephrine: (Moderate) Diuretics can cause decreased arterial responsiveness to norepinephrine, but the effect is not sufficient to preclude their coadministration.
    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.
    Olanzapine; Fluoxetine: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and fluoxetine use; consider discontinuing fluoxetine if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia. (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents.
    Olanzapine; Samidorphan: (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents.
    Oliceridine: (Moderate) Monitor patients for signs of diminished diuresis and/or effects on blood pressure if diuretics are used concomitantly with oliceridine; increase the dosage of the diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
    Olmesartan: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative.
    Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative. (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
    Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative. (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
    Olopatadine; Mometasone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
    Omeprazole: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and loop diuretic use due to risk for hypomagnesemia.
    Omeprazole; Amoxicillin; Rifabutin: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and loop diuretic use due to risk for hypomagnesemia.
    Omeprazole; Sodium Bicarbonate: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and loop diuretic use due to risk for hypomagnesemia.
    Oprelvekin, rh-IL-11: (Major) Patients receiving loop diuretics during oprelvekin, rh-IL-11 therapy are at increased risk for developing severe hypokalemia; close monitoring of fluid and electrolyte status is warranted during concurrent diuretic and oprelvekin therapy.
    Oxaprozin: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. 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.
    Oxybutynin: (Minor) Diuretics can increase urinary frequency, which may aggravate bladder symptoms.
    Oxycodone: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and oxycodone; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the 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 loop 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 loop diuretics who are susceptible to hypotension.
    Pamidronate: (Moderate) Because both loop diuretics and intravenously administered bisphosphonates (i.e., alendronate, ibandronate, pamidronate, and zoledronic acid) can cause a decrease in serum calcium, caution is advised when used concomitantly in the treatment of hypercalcemia of malignancy in order to avoid hypocalcemia. In patients with hypercalcemia of malignancy, the initial treatment typically includes the use of loop diuretics, in combination with saline hydration, however, diuretic therapy should not be employed prior to correction of hypovolemia and dehydration.
    Pancuronium: (Moderate) Concomitant use of neuromuscular blockers and loop diuretics may prolong neuromuscular blockade, possibly due to hypokalemia or alterations in potassium concentrations across the end-plate membrane.
    Pantoprazole: (Moderate) Monitor magnesium concentration before and periodically during concomitant pantoprazole and loop diuretic use due to risk for hypomagnesemia.
    Paroxetine: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and paroxetine use; consider discontinuing paroxetine if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
    Pasireotide: (Moderate) Cautious use of pasireotide and loop diuretics is advised as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pasireotide. Assess the patient's potassium and magnesium concentration before and periodically during pasireotide receipt. Correct hypokalemia and hypomagnesemia before pasireotide receipt.
    Pentamidine: (Moderate) Drugs that are associated with hypokalemia and/or hypomagnesemia such as loop diuretics should be used with caution in patients also receiving pentamidine. Since pentamidine may cause QT prolongation independently of electrolyte imbalances, the risk for cardiac arrhythmias is potentiated by the concomitant use of agents associated with electrolyte loss. .
    Pentazocine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when loop 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 loop 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) Discontinue the loop diuretic prior to starting perindopril, if possible, or start perindopril at a lower dose. Monitor blood pressure and renal function during concomitant use, particularly when doses are increased. Concomitant use may increase the risk for hypotension or renal failure.
    Perindopril; Amlodipine: (Major) Discontinue the loop diuretic prior to starting perindopril, if possible, or start perindopril at a lower dose. Monitor blood pressure and renal function during concomitant use, particularly when doses are increased. Concomitant use may increase the risk for hypotension or renal failure.
    Phenelzine: (Moderate) Monitor blood pressure during concomitant loop diuretic and phenelzine use due to risk for additive hypotension.
    Phentermine; Topiramate: (Moderate) Monitor potassium concentration before and during concomitant topiramate and loop diuretic use due to risk for additive hypokalemia. Topiramate can increase the risk of hypokalemia through its inhibition of carbonic anhydrase activity and concomitant use with loop diuretics may further potentiate potassium-wasting.
    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.
    Pimozide: (Moderate) Caution is advisable during concurrent use of pimozide and loop diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pimozide. Potassium deficiencies should be corrected prior to treatment with pimozide and normalized potassium levels should be maintained during treatment.
    Pioglitazone: (Minor) Bumetanide has been associated with hyperglycemia, possibly due to potassium depletion, and, glycosuria has been reported. Because of this, a potential pharmacodynamic interaction exists between bumetanide and all antidiabetic agents. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely.
    Pioglitazone; Glimepiride: (Minor) Bumetanide has been associated with hyperglycemia, possibly due to potassium depletion, and, glycosuria has been reported. Because of this, a potential pharmacodynamic interaction exists between bumetanide and all antidiabetic agents. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely.
    Pioglitazone; Metformin: (Minor) Bumetanide has been associated with hyperglycemia, possibly due to potassium depletion, and, glycosuria has been reported. Because of this, a potential pharmacodynamic interaction exists between bumetanide and all antidiabetic agents. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely.
    Piroxicam: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. 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.
    Polycarbophil: (Moderate) Loop diuretics may increase the risk of hypokalemia, especially in patients receiving prolonged therapy with laxatives such as calcium polycarbophil. Monitor serum potassium to determine the need for potassium supplementation and/or alteration in drug therapy.
    Polyethylene Glycol: (Moderate) Monitor renal function and serum electrolytes and ensure adequate hydration before and after concomitant loop diuretic and polyethylene glycol 3350 use. Concomitant use may increase the risk for fluid and electrolyte abnormalities and renal injury.
    Polyethylene Glycol; Electrolytes: (Moderate) Monitor renal function and serum electrolytes and ensure adequate hydration before and after concomitant loop diuretic and polyethylene glycol 3350 use. Concomitant use may increase the risk for fluid and electrolyte abnormalities and renal injury. (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) Monitor renal function and serum electrolytes and ensure adequate hydration before and after concomitant loop diuretic and polyethylene glycol 3350 use. Concomitant use may increase the risk for fluid and electrolyte abnormalities and renal injury. (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; Bisacodyl: (Moderate) Loop diuretics may increase the risk of hypokalemia especially in patients receiving prolonged therapy with laxatives. Monitor serum potassium levels to determine the need for potassium supplementation and/or alteration in drug therapy. (Moderate) Monitor renal function and serum electrolytes and ensure adequate hydration before and after concomitant loop diuretic and polyethylene glycol 3350 use. Concomitant use may increase the risk for fluid and electrolyte abnormalities and renal injury.
    Polymyxin B: (Moderate) Systemic polymyxin B is nephrotoxic and should be used cautiously with loop diuretics, which may cause azotemia and may increase the risk for renal toxicity when coadministered. Close monitoring of renal status and for drug toxicity is recommended. Diminishing urine output and a rising BUN are indications to discontinue systemic polymyxin B therapy.
    Pramlintide: (Minor) Loop diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between these drugs and all antidiabetic agents. Monitor patient for diabetic control.
    Prazosin: (Moderate) The first dose response (acute postural hypotension) of prazosin may be exaggerated in patients who are receiving loop diuretics. This effect can be minimized by reducing the prazosin dose to 1 to 2 mg three times a day, by introducing the loop diuretic cautiously, and then by retitrating prazosin to clinical response.
    Prednisolone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
    Prednisone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
    Prilocaine; Epinephrine: (Moderate) Monitor blood pressure, heart rate, and serum potassium during concomitant epinephrine and loop diuretic use. Loop diuretics may antagonize the pressor effects and potentiate the arrhythmogenic and hypokalemic effects of epinephrine.
    Probenecid: (Moderate) Probenecid can interfere with the natriuresis and plasma renin activity increases caused by diuretics such as bumetanide. Bumetanide can in turn increase the levels of serum uric acid, antagonizing the effects of probenecid.
    Probenecid; Colchicine: (Moderate) Probenecid can interfere with the natriuresis and plasma renin activity increases caused by diuretics such as bumetanide. Bumetanide can in turn increase the levels of serum uric acid, antagonizing the effects of probenecid.
    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.
    Promethazine; 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.
    Propofol: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
    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.
    Pseudoephedrine; Triprolidine: (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.
    Psyllium: (Moderate) Loop diuretics may increase the risk of hypokalemia especially in patients receiving prolonged therapy with laxatives. Monitor serum potassium levels to determine the need for potassium supplementation and/or alteration in drug therapy.
    Quinapril: (Major) Discontinue the loop diuretic prior to starting quinapril, if possible, or start quinapril at the lower dose of 5 mg/day. Monitor blood pressure and renal function during concomitant use, particularly when doses are increased. Concomitant use may increase the risk for hypotension or renal failure.
    Quinapril; Hydrochlorothiazide, HCTZ: (Major) Discontinue the loop diuretic prior to starting quinapril, if possible, or start quinapril at the lower dose of 5 mg/day. Monitor blood pressure and renal function during concomitant use, particularly when doses are increased. Concomitant use may increase the risk for hypotension or renal failure. (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
    Quinidine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Rabeprazole: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with loop diuretics (furosemide, bumetanide, torsemide, and ethacrynic acid). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
    Ramipril: (Major) Discontinue the loop diuretic prior to starting ramipril, if possible, or start ramipril at a lower dose. Monitor blood pressure and renal function during concomitant use, particularly when doses are increased. Concomitant use may increase the risk for hypotension or renal failure.
    Rapacuronium: (Moderate) Concomitant use of neuromuscular blockers and loop diuretics may prolong neuromuscular blockade, possibly due to hypokalemia or alterations in potassium concentrations across the end-plate membrane.
    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.
    Repaglinide: (Minor) Loop diuretics have been associated with hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between loop diuretics and all antidiabetic agents. Monitor for a loss of diabetic control.
    Risperidone: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
    Rocuronium: (Moderate) Concomitant use of neuromuscular blockers and loop diuretics may prolong neuromuscular blockade, possibly due to hypokalemia or alterations in potassium concentrations across the end-plate membrane.
    Rosiglitazone: (Minor) Bumetanide has been associated with hyperglycemia, possibly due to potassium depletion, and, glycosuria has been reported. Because of this, a potential pharmacodynamic interaction exists between bumetanide and all antidiabetic agents. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely.
    Sacubitril; Valsartan: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative.
    Salicylates: (Moderate) Salicylates may decrease the diuretic, natriuretic, and antihypertensive actions of diuretics, possibly through inhibition of renal prostaglandin synthesis. Patients receiving loop diuretics and salicylates should be monitored for changes in the effectiveness of their diuretic therapy.
    Saxagliptin: (Minor) Bumetanide has been associated with hyperglycemia, possibly due to potassium depletion, and, glycosuria has been reported. Because of this, a potential pharmacodynamic interaction exists between bumetanide and all antidiabetic agents. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely.
    Semaglutide: (Minor) Loop diuretics, such as bumetanide, furosemide, and torsemide, may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between these drugs and all antidiabetic agents, including incretin mimetics. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if these drugs are initiated.
    Senna: (Minor) The risk of hypokalemia due to loop diuretics may be increased in patients receiving prolonged therapy with certain laxatives. Monitor serum potassium levels to determine the need for potassium supplementation and/or alteration in drug therapy in patients receiving loop diuretics. Senna rarely causes hypokalemia with proper use.
    Serotonin norepinephrine reuptake inhibitors: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and serotonin norepinephrine reuptake inhibitor (SNRI) use; consider discontinuing the SNRI if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
    Sertraline: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and sertraline use; consider discontinuing sertraline if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing 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.
    Simvastatin; Sitagliptin: (Minor) Bumetanide has been associated with hyperglycemia, possibly due to potassium depletion, and, glycosuria has been reported. Because of this, a potential pharmacodynamic interaction exists between bumetanide and all antidiabetic agents. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely.
    Sitagliptin: (Minor) Bumetanide has been associated with hyperglycemia, possibly due to potassium depletion, and, glycosuria has been reported. Because of this, a potential pharmacodynamic interaction exists between bumetanide and all antidiabetic agents. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely.
    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. In addition, loop diuretics may increase the risk of hypokalemia especially in patients receiving prolonged therapy with laxatives. Monitor serum potassium levels to determine the need for potassium supplementation and/or alteration in drug therapy.
    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.
    Sodium Polystyrene Sulfonate: (Moderate) Sodium polystyrene sulfonate should be used cautiously with other agents that can induce hypokalemia such as loop diuretics, insulins, or intravenous sodium bicarbonate. Because of differences in onset of action, sodium polystyrene sulfonate is often used with these agents. With appropriate monitoring, hypokalemia can be avoided.
    Solifenacin: (Minor) Diuretics can increase urinary frequency, which may aggravate bladder symptoms. Risk versus benefit should be addressed in patients receiving diuretics and solifenacin.
    Sorbitol: (Moderate) Loop diuretics may increase the risk of hypokalemia especially in patients receiving prolonged therapy with laxatives. Monitor serum potassium levels to determine the need for potassium supplementation and/or alteration in drug therapy.
    Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
    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.
    Succinylcholine: (Moderate) Concomitant use of neuromuscular blockers and loop diuretics may prolong neuromuscular blockade, possibly due to hypokalemia or alterations in potassium concentrations across the end-plate membrane.
    Sufentanil: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when loop diuretics are 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.
    Sulfonylureas: (Minor) Bumetanide has been associated with hyperglycemia, possibly due to potassium depletion, and, glycosuria has been reported. Because of this, a potential pharmacodynamic interaction exists between bumetanide and all antidiabetic agents. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely.
    Sulindac: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. 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.
    Sumatriptan; Naproxen: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. 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.
    Tapentadol: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when loop 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.
    Telavancin: (Moderate) Concurrent or sequential use of telavancin with other potentially nephrotoxic drugs such as loop diuretics may lead to additive nephrotoxicity. Closely monitor renal function and adjust telavancin doses based on calculated creatinine clearance.
    Telmisartan: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative.
    Telmisartan; Amlodipine: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative.
    Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative. (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
    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.
    Thiazide diuretics: (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
    Thiazolidinediones: (Minor) Bumetanide has been associated with hyperglycemia, possibly due to potassium depletion, and, glycosuria has been reported. Because of this, a potential pharmacodynamic interaction exists between bumetanide and all antidiabetic agents. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely.
    Thiothixene: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Tirzepatide: (Minor) Loop diuretics, such as bumetanide, furosemide, and torsemide, may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between these drugs and all antidiabetic agents, including incretin mimetics. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if these drugs are initiated.
    Tizanidine: (Moderate) Monitor blood pressure during concomitant loop diuretic and tizanidine use due to risk for additive hypotension.
    Tolmetin: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. 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.
    Tolterodine: (Minor) Diuretics can increase urinary frequency, which may aggravate bladder symptoms.
    Tolvaptan: (Moderate) Monitor serum sodium closely if tolvaptan and bumetanide are used together. Coadministration increases the risk of too rapid correction of serum sodium.
    Topiramate: (Moderate) Monitor potassium concentration before and during concomitant topiramate and loop diuretic use due to risk for additive hypokalemia. Topiramate can increase the risk of hypokalemia through its inhibition of carbonic anhydrase activity and concomitant use with loop diuretics may further potentiate potassium-wasting.
    Tramadol: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and tramadol; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
    Tramadol; Acetaminophen: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and tramadol; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
    Trandolapril: (Major) Discontinue the loop diuretic prior to starting trandolapril, if possible, or start trandolapril at the lower dose of 0.5 mg/day. Monitor blood pressure and renal function during concomitant use, particularly when doses are increased. Concomitant use may increase the risk for hypotension or renal failure.
    Trandolapril; Verapamil: (Major) Discontinue the loop diuretic prior to starting trandolapril, if possible, or start trandolapril at the lower dose of 0.5 mg/day. Monitor blood pressure and renal function during concomitant use, particularly when doses are increased. Concomitant use may increase the risk for hypotension or renal failure.
    Tranylcypromine: (Contraindicated) 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: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
    Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
    Trospium: (Minor) Diuretics can increase urinary frequency, which may aggravate bladder symptoms.
    Valsartan: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative.
    Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative. (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
    Vecuronium: (Moderate) Concomitant use of neuromuscular blockers and loop diuretics may prolong neuromuscular blockade, possibly due to hypokalemia or alterations in potassium concentrations across the end-plate membrane.
    Venlafaxine: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and serotonin norepinephrine reuptake inhibitor (SNRI) use; consider discontinuing the SNRI if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing 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.
    Vorinostat: (Moderate) Use vorinostat and loop diuretics together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Loop diuretics may cause electrolyte imbalances including low potassium; hypomagnesemia, hypokalemia, or hypocalcemia may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
    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.
    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) Monitor potassium and magnesium levels when loop diuretics are used during ziprasidone therapy. The risk of QT prolongation from ziprasidone is increased in the presence of hypokalemia or hypomagnesemia.
    Zoledronic Acid: (Moderate) Loop diuretics should be used with caution in combination with zoledronic acid in order to avoid hypocalcemia. In patients with hypercalcemia of malignancy, the initial treatment typically includes the use of loop diuretics, in combination with saline hydration, however, diuretic therapy should not be employed prior to correction of hypovolemia and dehydration.

    PREGNANCY AND LACTATION

    Pregnancy

    There are no adequate and well-controlled studies of bumetanide in pregnant women. A small investigational experience and marketing experience have not indicated any evidence of adverse effects on the fetus; however, these data do not rule out the possibility of harmful effects. Use bumetanide during pregnancy only if the potential benefit justifies the potential risk to the fetus. Bumetanide has been shown to be nonteratogenic, but it has a slight embryocidal effect in rats when given in doses of 3,400 times the maximum human therapeutic dose (MRHD) and in rabbits at doses of 3.4 times the MRHD. Moderate growth retardation and increased incidence of delayed ossification of sternebrae were observed in rats at oral doses of 100 mg/kg/day (3,400 times the MRHD); these adverse effects were not observed at doses of 30 mg/kg/day (1,000 times the MRHD).[28620]

    It is not known whether bumetanide is excreted in human milk. Avoid breast-feeding during bumetanide therapy since it may be excreted in human milk.[28620] Potent diuretics such as bumetanide may suppress lactation as a result of intense diuresis. Of note, previous American Academy of Pediatrics (AAP) recommendations considered bendroflumethiazide, chlorthalidone, chlorothiazide, and hydrochlorothiazide to be usually compatible with breast-feeding.[27500]

    MECHANISM OF ACTION

    Bumetanide is a loop diuretic that inhibits sodium and chloride resorption by competing with chloride for the Na+/K+/2Cl- co-transporter in the ascending limb of the loop of Henle. Bumetanide may also act on the proximal tubule, as phosphate reabsorption occurs primarily in the proximal tubule and phosphaturia occurs with bumetanide therapy. A profound diuresis results from the increased urinary excretion of sodium, chloride, potassium, and hydrogen ions. Additionally, bumetanide causes increased urinary excretion of calcium, magnesium, bicarbonate, ammonium, and phosphate. The diuresis caused by bumetanide can lead to increased aldosterone production, resulting in increased sodium resorption and increased potassium and hydrogen excretion. Excessive loss of these electrolytes can lead to metabolic alkalosis.
     
    Bumetanide substantially increases renal blood flow by dilating the renal vasculature. Initially, diuretics lower blood pressure by causing hypovolemia (decreased plasma and extracellular fluid), temporarily increasing the glomerular filtration rate and decreasing cardiac output. Cardiac output eventually returns to normal, but a reduction in peripheral resistance is maintained, resulting in lower blood pressure.

    PHARMACOKINETICS

    Bumetanide is administered orally, intramuscularly, or intravenously. The duration of action is 3—6 hours. Bumetanide is 96% plasma protein-bound. It is not clear whether the drug crosses the placenta, enters the CSF, or appears in breast milk. Bumetanide is metabolized in the liver to at least five metabolites, with 80% of a dose excreted in the urine (45% unchanged), and 10—20% excreted in the feces. The half-life of bumetanide is 1—1.5 hours. 

    Oral Route

    Following oral administration, bumetanide is 85—95% absorbed. Food will delay oral absorption but will not alter the diuretic response. Diuresis generally begins 30—60 minutes after oral administration. Peak effects occur within 1—2 hours after oral administration. 

    Intravenous Route

    Diuresis generally begins within several minutes after IV administration of bumetanide. Peak effects occur within 15—30 minutes after IV administration.

    Intramuscular Route

    Diuresis generally begins 40 minutes after IM administration of bumetanide.