PDR MEMBER LOGIN:
  • PDR Search

    Required field
  • Advertisement
  • CLASSES

    Loop Diuretics

    DEA CLASS

    Rx

    DESCRIPTION

    Oral and parenteral loop diuretic
    Used for the management of edema associated with congestive heart failure, cirrhosis, and renal disease, pulmonary edema, and hypertension
    Available as a subcutaneous on-body Infusor for treatment of congestion due to fluid overload in NYHA Class II or III chronic heart failure

    COMMON BRAND NAMES

    Delone, FUROSCIX, Lasix

    HOW SUPPLIED

    Delone/Furosemide/Lasix Oral Tab: 20mg, 40mg, 80mg
    FUROSCIX Subcutaneous Inj Sol: 1mL, 8mg
    Furosemide Intramuscular Inj Sol: 1mL, 10mg
    Furosemide Intravenous Inj Sol: 1mL, 10mg
    Furosemide Oral Sol: 1mL, 5mL, 10mg, 40mg

    DOSAGE & INDICATIONS

    For the treatment of peripheral edema or edema associated with heart failure, chronic lung disease (CLD), or nephrotic syndrome.
    For the treatment of congestion due to fluid overload in adult patients with New York Heart Association (NYHA) Class II or Class III chronic heart failure.
    NOTE: Subcutaneous furosemide infusion is not indicated for emergency use or in patients with acute pulmonary edema.
    Subcutaneous dosage (Furoscix)
    Adults

    80 mg subcutaneously infused over 5 hours via a pre-programmed on-body infusor (30 mg delivered over the first hour followed by 12.5 mg per hour for the following 4 hours). Not indicated for chronic use; replace with oral diuretics as soon as clinically practical.

    Oral dosage
    Adults

    20 to 80 mg PO once, initially. May repeat the dose or increase by 20 to 40 mg/dose every 6 to 8 hours as needed until the desired diuretic effect is attained. Usual dose: 40 to 240 mg/day in 1 to 2 divided doses. Max: 600 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

    1 to 2 mg/kg/dose PO every 6 to 12 hours, initially; may increase dose by 1 to 2 mg/kg/dose (Max: 6 mg/kg/dose) after 6 to 8 hours if needed to achieve desired diuretic effect. Adjust dose to minimum effective dose for maintenance; large doses are not recommended for chronic use. Alternatively, for the management of nephrotic syndrome, some experts recommend 1 to 2 mg/kg/day PO in 1 or 2 divided doses.

    Premature and Term Neonates older than 32 weeks postconceptional age

    1 to 2 mg/kg/dose PO 1 to 2 times daily, initially. Use the lowest effective dose.

    Premature Neonates 32 weeks postconceptional age or younger

    1 to 2 mg/kg/dose PO initially. Because of the risk for accumulation, chronic doses should not be administered more frequently than every 24 hours. Bioavailability is variable.

    Intermittent Intravenous or Intramuscular dosage
    Adults

    20 to 40 mg IV or IM once, initially. May repeat the dose or increase by 20 mg/dose every 2 hours as needed until the desired diuretic effect is attained. This individually determined dose should be administered once or twice daily. 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 2 mg/kg/dose IV or IM every 6 to 12 hours. If the diuretic response is not adequate after 2 hours, increase the dose by 1 mg/kg/dose (Max: 6 mg/kg/dose). Use the lowest effective dose. Typical Max = 20 mg for those not chronically on loop diuretics.

    Premature and Term Neonates older than 32 weeks postconceptional age

    1 to 2 mg/kg/dose IV or IM every 12 to 24 hours. Use the lowest effective dose.

    Premature Neonates 32 weeks postconceptional age or younger

    1 mg/kg/dose IV. Because of the risk for accumulation, doses should not be administered more frequently than every 24 hours.

    Continuous Intravenous Infusion dosage†
    Adults

    40 mg IV bolus, then 10 to 40 mg/hour continuous IV infusion. 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).

    Adolescents

    Specific dosing information for adolescents is not available; however, 0.1 mg/kg IV load followed an infusion of 0.1 to 0.4 mg/kg/hour IV has been used for short durations in children after cardiac surgery and a 40 mg IV load followed by an infusion of 10 to 40 mg/hour is recommended in adult patients with chronic heart failure.

    Infants and Children

    0.1 mg/kg (Min: 1 mg) IV load followed by an infusion of 0.1 mg/kg/hour has been studied for short durations (24 hours or less) in postoperative cardiac patients. The infusion was doubled every 2 hours to a maximum of 0.4 mg/kg/hour in patients whose urine output remained less than 1 mL/kg/hour. Compared to patients receiving intermittent IV doses, patients receiving continuous infusions had a greater urine output per dose of drug, less variability in urine output, and lower urinary losses of sodium and chloride.

    Neonates

    0.1 mg/kg (Min: 1 mg) IV load followed by an infusion of 0.1 mg/kg/hour has been studied for short durations (24 hours or less) in postoperative cardiac patients. The infusion was doubled every 2 hours to a maximum of 0.4 mg/kg/hour in patients whose urine output remained less than 1 mL/kg/hour. Compared to patients receiving intermittent IV doses, patients receiving continuous infusions had a greater urine output per dose of drug, less variability in urine output, and lower urinary losses of sodium and chloride.

    For the management of pulmonary edema or prevention of adverse hemodynamic effects associated with blood product transfusions†.
    For the adjunctive treatment of acute pulmonary edema.
    Intravenous or Intramuscular dosage
    Adults

    Initially, 40 mg IV injected slowly (over 1 to 2 minutes). If satisfactory response not achieved within 1 hour, the dose may be increased to 80 mg IV injected slowly.

    Infants, Children, and Adolescents†

    1 to 2 mg/kg/dose IV or IM every 6 to 12 hours. If the diuretic response is not adequate after 2 hours, increase the dose by 1 mg/kg/dose (Max: 6 mg/kg/dose). Use the lowest effective dose. Typical Max = 20 mg for those not chronically on loop diuretics.

    Premature and Term Neonates older than 32 weeks postconceptional age†

    1 to 2 mg/kg/dose IV or IM every 12 to 24 hours. Use the lowest effective dose.

    Premature Neonates 32 weeks postconceptional age and younger†

    1 mg/kg/dose IV. Because of the risk for accumulation, doses should not be administered more frequently than every 24 hours.

    For the prevention of adverse hemodynamic effects and/or pulmonary edema associated with blood product transfusions†.
    Intravenous dosage
    Adults

    40 mg IV given immediately before whole blood transfusions was found to prevent a significant increase in pulmonary capillary wedge pressure (PCWP) in 2 small prospective trials of patients with chronic severe anemia. In both trials, 1 unit of whole blood was administered at a rate of 5 mL/minute in the furosemide groups with no observed increase in PCWP after the transfusion. The control group received 1 unit of whole blood at a rate of 5 mL/minute in the first trial and 2, 5, or 10 mL/minute in the second trial . The authors reported an increase in PCWP in all control groups after the transfusions.

    Premature Neonates†

    Although use in clinical practice is not uncommon, limited published data are available evaluating furosemide prior to or after the administration of blood products. One prospective, unblinded trial evaluated furosemide 1 mg/kg IV after transfusions of 10 mL/kg of packed red blood cells (PRBC) in 24 cases; 3 of the 21 infants were studied twice. The infants were 6.1 +/- 2.9 weeks of age (32.5 +/- 3.4 weeks mean gestational age at birth) and all had bronchopulmonary dysplasia. The PRBCs were administered at a rate of 5 mL/kg/hour, and furosemide was given in 16 of the 24 cases. The infants that received furosemide demonstrated an improvement in lung compliance, tidal volume, and minute ventilation compared to baseline. There was no observed improvement in these values in the untreated group. The authors noted no difference in the clinical respiratory status between the 2 groups. Some authors caution against the routine use of furosemide following PRBC transfusions due to a lack of efficacy data and the potential for electrolyte imbalance.

    For adjunctive treatment of edema in patients with acute or chronic renal failure (renal impairment).
    Oral dosage
    Adults

    Initially, 80 mg PO once daily, increasing in increments of 80 to 120 mg/day until desired clinical response. For immediate diuresis, 320 to 400 mg once daily has been suggested.

    Infants, Children, and Adolescents

    Initially, 1 to 2 mg/kg/dose PO every 6 to 12 hours. If response is not adequate 6 to 8 hours after the dose, increase by 1 to 2 mg/kg/dose (Max: 6 mg/kg/dose). Adjust to minimum effective dose for maintenance; large doses are not recommended for chronic use.

    Premature and Term Neonates older than 32 weeks postconceptional age

    Initially, 1 to 2 mg/kg/dose PO, given 1 to 2 times daily. Bioavailability is variable.

    Premature Neonates 32 weeks postconceptional age and younger

    Initially, 1 to 2 mg/kg/dose PO. Because of the risk for accumulation, chronic doses should not be administered more frequently than every 24 hours. Bioavailability is variable.

    Intravenous dosage
    Adults

    Initially, 100 to 200 mg IV. Traditionally, it has been recommended that doses can be doubled every 2 to 24 hours until desired clinical response, however, most clinicians would probably consider 600 to 800 mg a maximum dose and either administer a different loop-active agent, or add a second agent in combination with furosemide. A maximum infusion rate of 4 mg/minute has been recommended for doses greater than 120 mg or for patients with cardiac or renal failure.

    Infants, Children, and Adolescents

    1 to 2 mg/kg/dose IV or IM every 6 to 12 hours. If the diuretic response is not adequate after 2 hours, increase the dose by 1 mg/kg/dose IV (Max: 6 mg/kg/dose IV). Use the lowest effective dose.

    Premature and Term Neonates older than 32 weeks postconceptional age

    1 to 2 mg/kg/dose IV or IM every 12 to 24 hours. Use the lowest effective dose.

    Premature Neonates 32 weeks postconceptional age and younger

    1 mg/kg/dose IV. Because of the risk for accumulation, doses should not be administered more frequently than every 24 hours.

    For the treatment of hypertension.
    Oral dosage
    Adults

    40 mg PO twice daily, initially. May increase dose if further control is needed. Usual dose range: 20 to 80 mg/day. Max: 600 mg/day.

    Infants†, Children†, and Adolescents†

    0.5 to 2 mg/kg/dose PO in 1 to 2 divided doses, initially. The FDA-approved dose for the treatment of edema is 1 to 2 mg/kg/dose PO every 6 to 12 hours, initially. May increase dose by 1 to 2 mg/kg/dose if further control is needed. Max: 6 mg/kg/dose.

    For adjunctive treatment of hypertensive urgency† or hypertensive emergency†.
    Intravenous dosage
    Adults

    Doses of 40—80 mg IV have been used in patients with normal renal function.

    Geriatric

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

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

    Initially, 80—100 mg IV or IM; repeat the dose every 1—2 hours as needed based on clinical response. Less severe cases may use smaller doses every 2—4 hours. Initiate saline administration before the first dose of furosemide to avoid volume contraction which may limit the desired calciuric response.

    Geriatric

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

    Children

    Initially, 25—50 mg IV or IM. The dose may be repeated every 4 hours as needed based on clinical response. Initiate saline administration before the first dose of furosemide to avoid volume contraction which may limit the desired calciuric response.

    For the treatment of ascites† in combination with spironolactone or amiloride.
    Oral dosage
    Adults

    Initially, 40 mg PO once daily, in the morning in combination with spironolactone; dose may be increased after 2—3 days if no clinical response.

    Geriatric

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

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    600 mg/day PO or 6 g/day IV infusion. Up to 4 g/day PO has been given to treat chronic renal failure. 80 mg/dose subcutaneously via On-Body Infusor (Furoscix).

    Geriatric

    600 mg/day PO or 6 g/day IV infusion. Up to 4 g/day PO has been given to treat chronic renal failure. 80 mg/dose subcutaneously via On-Body Infusor (Furoscix).

    Adolescents

    6 mg/kg/dose PO/IV. Safety and efficacy have not been established for subcutaneous on-body infuser (Furoscix).

    Children

    6 mg/kg/dose PO/IV. Safety and efficacy have not been established for subcutaneous on-body infuser (Furoscix).

    Infants

    6 mg/kg/dose PO/IV. Safety and efficacy have not been established for subcutaneous on-body infuser (Furoscix).

    Neonates

    Premature and Term Neonates older than 32 weeks postconceptional age: 2 mg/kg/dose IV every 12 hours; the maximum PO dose has not been established in neonates. Safety and efficacy have not been established for subcutaneous on-body infuser (Furoscix).
    Premature Neonates 32 weeks postconceptional age and younger: 1 mg/kg/dose IV every 24 hours; the maximum PO dose has not been established in neonates. Safety and efficacy have not been established for subcutaneous on-body infuser (Furoscix).

    DOSING CONSIDERATIONS

    Hepatic Impairment

    No specific dosage adjustment is needed; see the dosage for the treatment of ascites. Diuretics should be used with caution in patients with hepatic disease since minor alterations of fluid and electrolyte balance may precipitate hepatic coma.

    Renal Impairment

    No specific dosage adjustments are recommended. Higher doses with extended dosage intervals may be effective in patients with end-stage renal disease (ESRD).

    ADMINISTRATION

    Oral Administration

    Administer with meals to minimize indigestion and gastrointestinal irritation.

    Oral Solid Formulations

    If patient has difficulty swallowing, furosemide tablets may be crushed.

    Oral Liquid Formulations

    When administering furosemide to an infant or child using a medicine dropper or oral syringe, slowly squirt the solution into the side of the child's mouth so that he or she will swallow the liquid naturally. Do not squirt onto the back of the throat because this may cause gagging. Rinse the dropper or syringe in warm water after each use.

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intravenous Administration

    Dilution
    Dilute in 0.9% Sodium Chloride Injection, Lactated Ringer's Injection, or 5% Dextrose Injection; adjust pH to more than 5.5 when necessary.
    ASHP Recommended Standard Concentrations for Adult Continuous Infusions: 2 mg/mL or 10 mg/mL.
    ASHP Recommended Standard Concentrations for Pediatric Continuous Infusions: 2 mg/mL or 10 mg/mL.
     
    IV Push
    No dilution necessary.
    Inject each 20 to 40 mg of furosemide slowly IV over 1 to 2 minutes.
    In pediatric patients, injection no faster than 0.5 mg/kg/minute; more rapid administration increased the risk of ototoxicity.
    For patients receiving extracorporeal membrane oxygenation (ECMO), administer IV furosemide outside the circuit; the drug is substantially adsorbed by circuit components.
     
    Intermittent IV Infusion
    Infuse at a rate not to exceed 0.5 mg/kg/minute or for high dose therapy, do not exceed 4 mg/minute.
     
    Continuous IV Infusion
    NOTE: Furosemide is not FDA-approved for continuous IV administration.
    Infuse at a rate not to exceed 4 mg/minute in adults or 0.5 mg/kg/minute in children.
    The risk of ototoxicity increases with more rapid parenteral administration.

    Intramuscular Administration

    No dilution necessary.
    Inject deeply into a large muscle mass (e.g., anterolateral thigh or deltoid [children and adolescents only]).

    Subcutaneous Administration

    Subcutaneous furosemide infusion via On-Body Infusor (Furoscix):
    Prior to preparing or applying the on-body infusor, read and become familiar with the manufacturer's 'Instructions for Use'.
    During the 5-hour subcutaneous infusion, limit activity, especially bending movements, and avoid riding in a car or flying in an airplane.
    Do not use the on-body infusor within 12 inches of mobile phones, tablets, computers or wireless accessories (e.g. TV remote control, computer keyboard or mouse).
    Do not get the infusor wet. Avoid showering, bathing, swimming, and participating in activities that result in sweating.
    If the indicator light blinks red and the on-body infusor beeps, the on-body infusor has either experienced an internal error or come off of the skin. Do not use the on-body infusor. If the on-body infusor is on the skin, instruct patients to carefully remove it and contact their care team for further instructions.
     
    Preparation:
    Wash hands prior to handling the on-body infusor. Gather all materials (on-body infusor carton [contains on-body infusor, prefilled cartridge, instructions for use, and alcohol wipes], sharps container, and, if needed, hair clippers) and place on a clean surface.
    Open the carton to remove supplies, check for any damage to either the on-body infusor or prefilled cartridge, and check the solution in the prefilled cartridge. The furosemide solution should be clear to slightly yellow; do not use if liquid is discolored, cloudy, or contains particulates. Do not use the on-body infusor or prefilled cartridge if either item appears to be damaged.
    Clean the tip (small end) of the prefilled cartridge with an alcohol wipe. Turn on the on-body infusor by fully opening the cartridge holder; a beeping sound and blue blinking light indicate that the on-body infusor is turned on. Begin subcutaneous infusion within 30 minutes of fully opening the cartridge holder or the on-body infusor will alarm and not restart.
    Insert the prefilled cartridge into the cartridge holder with the tip pointed down. The cartridge should easily slide into position; however, if it does not, check the cartridge to verify that the tip is pointed down and try again.
    Once cartridge installed, close the cartridge holder until it is even with the rest of the on-body infusor. If there is a beeping sound and a red blinking light, the infusor has experienced an internal error and should not be used.
    Do not hit the blue start button until the infusor has been applied to the skin and patient is ready for the infusion to begin.
     
    Application:
    Select a flat, hairless or nearly hairless application site on the abdomen. The site should be on either side of the belly button (navel), below the rib cage and above the belt line. The distance from the top of the belt line to the bottom of the ribcage should be at least 2.5 inches. If needed, remove excess hair by shaving or clipping the hair prior to infusor application. Do not select a site where belts, waistbands, or other types of clothing may rub against, disturb, or dislodge the on-body infusor.
    Wipe the selected area with an alcohol wipe and allow the area to dry. Avoid application of lotions, oils, or ointments to the abdomen prior to applying the on-body infusor. Rotate the site of subcutaneous administration with each application.
    Remove the adhesive liner from the on-body infusor by grasping the white tab and pulling it away from the blue tab and adhesive backing. Position the infusor such that the cartridge window and indicator light may be seen during the infusion.
    While standing or sitting straight up, apply on-body infusor to a clean, dry, area of the abdomen that is not tender, bruised, red, or indurated. Do not bend over when applying the on-body infusor. Avoid touching the adhesive side or letting it touch other objects or surfaces prior to applying the infusor.
    Firmly press the on-body infusor onto the skin and hold it in place for several seconds. Next, rub fingers over the edges of the adhesive to ensure that it is adequately stuck to the skin. Once applied to the skin, do not attempt to remove and reapply the infusor, as the adhesive may not work as well.
    To start the infusion, firmly press and release the blue start button. A beeping sound and green light indicate that the needle has been placed and the subcutaneous infusion has begun; the infusion motor may also be heard. During the 5-hour infusion, the green indicator light will periodically blink to signify that furosemide is infusing.
    To prevent infusion disruption or infusor displacement, limit activity and avoid exercise until completion of the infusion.
    If the on-body infusor falls off or if the indicator light blinks red, instruct patients to call their care team immediately. If the infusor is on the skin, it should be carefully removed. Do not reapply or reuse the on-body infusor.
    When the infusion is complete, the indicator light will turn solid green, the white plunger rod will fill the cartridge window, and there will be a beeping sound. The infusor may now be removed.
    To remove the infusor, hold the surrounding skin down while pulling on the blue tab. As the on-body infusor is removed, the indicator light will turn off, a needle cover will extend over the needle, and the infusor will turn off.
    Dispose the used on-body infusor with the cartridge into an appropriate sharps container. Do not attempt to remove the cartridge from the infusor, as it cannot be removed.
    Storage: Store the subcutaneous furosemide on-body infusor at controlled room temperature between 20 and 25 degrees C (68 and 77 degrees F). Do not refrigerate or freeze. Keep the prefilled cartridge in the original carton until it is to be used. Protect from light. Begin subcutaneous infusion within 30 minutes of fully opening the cartridge holder.

    STORAGE

    Generic:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Discard unused portion. Do not store for later use.
    - Protect from light
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Delone :
    - Avoid exposure to heat
    - Protect from direct sunlight
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    FUROSCIX:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Do not freeze
    - Do not refrigerate
    - Protect from light
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    - Store in a dry place
    - Store in carton until time of use
    Lasix:
    - Avoid exposure to heat
    - Protect from direct sunlight
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Sulfonamide hypersensitivity, thiazide diuretic hypersensitivity

    Furosemide is contraindicated in patients with known hypersensitivity to this drug.   Because cross-sensitivity with furosemide has rarely been observed, bumetanide can be substituted for furosemide in patients allergic to furosemide. Subcutaneous furosemide infusion is contraindicated in patients with a known hypersensitivity to medical adhesives. 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 furosemide is a sulfonamide derivative, sulfonamide cross-sensitivity has rarely been 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. Furosemide 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 to 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

    Furosemide may cause fluid, electrolyte and metabolic abnormalities such as hyponatremia, hypokalemia, hypocalcemia, hypochloremia, and hypomagnesemia. Patients receiving higher doses of furosemide, patients with inadequate oral intake and elderly patients are at increased risk for these fluid and electrolyte imbalances.   Loop diuretics may induce metabolic alkalosis associated with hypokalemia and hypochloremia; this acid/base imbalance is effectively treated with potassium chloride replacement. Serum electrolytes and CO2 should be monitored frequently during furosemide therapy.

    Diabetes mellitus, hyperglycemia

    Assess blood and urine glucose levels in patients with diabetes mellitus or hyperglycemia during treatment with furosemide; loop diuretics can impair glucose tolerance.

    Diarrhea, heart failure, ventricular arrhythmias

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

    Acute myocardial infarction

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

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

    Furosemide is contraindicated in patients with anuria. Use furosemide cautiously in any patient with renal disease, such as severe renal impairment or renal failure. Dehydration and azotemia can occur from furosemide therapy. If increasing azotemia and oliguria occur during treatment of severe progressive renal disease, furosemide should be discontinued. Excessive diuresis may result in dehydration and decreased blood volume leading to circulatory collapse and possible development of vascular thrombosis and embolism, primarily in elderly patients. Renal function (BUN and creatinine) should be frequently monitored during furosemide therapy. The presence of hypoproteinemia (e.g., nephrotic syndrome) may weaken the effect of furosemide and increase its potential for ototoxicity. The risk of ototoxicity may also be increased when furosemide is administered to patients with severe renal impairment. Furosemide is an effective diuretic for many patients with renal impairment. Renal impairment may reduce clearance and warrant the use of higher doses with extended dosing intervals. Furosemide may be less effective in these patients and delayed excretion of drug may increase the risk of toxicity.

    Hypotension, orthostatic hypotension, sympathectomy, syncope

    Patients with pre-existing hypovolemia or hypotension should have their condition corrected before furosemide 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.

    Systemic lupus erythematosus (SLE)

    Furosemide has been reported to activate or exacerbate systemic lupus erythematosus (SLE), although the association is less certain than with procainamide or other drugs.

    Gout, hyperuricemia

    Since furosemide can reduce the clearance of uric acid, patients with gout or hyperuricemia can have exacerbations of their disease. Uric acid should be monitored frequently during furosemide therapy.

    Hearing impairment

    High doses and accumulation of furosemide may cause ototoxicity. Use furosemide with caution in patients with hearing impairment. Do not exceed the recommended rate of infusion when IV doses are administered. Hearing loss has been reported in newborn infants, including premature infants, receiving furosemide therapy. Premature infants with post conceptual age less than 31 weeks receiving doses exceeding 1 mg/kg/24 hours may develop plasma levels associated with potential toxic effects, including ototoxicity.

    Pancreatitis

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

    Pregnancy

    Published data from observational studies, case reports, and postmarketing reports have not demonstrated a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes with furosemide use during pregnancy according to the parenteral furosemide product label. However, the oral furosemide product label includes a recommendation to avoid furosemide use during pregnancy unless the potential benefit justifies the potential risk to the fetus. Due to the risk for higher birth weights, monitor fetal growth with furosemide therapy during pregnancy. Furosemide has been shown to cause unexplained maternal deaths and abortions in rabbits at 2, 4, and 8 times the maximum recommended human dose. Data from these studies involving rabbits indicate that fetal lethality may precede maternal deaths. In studies involving pregnant mice and rabbits, an increased incidence and severity of hydronephrosis (distension of the renal pelvis and, in some cases, ureters) was observed in fetuses exposed to furosemide during pregnancy compared fetuses not exposed to furosemide.[28429]

    Breast-feeding

    Use caution when administering furosemide to a breast-feeding mother. Furosemide is excreted in human breast milk. In addition, furosemide may suppress lactation as a result of intense diuresis. Previous American Academy of Pediatrics (AAP) recommendations considered chlorthalidone, chlorothiazide, and hydrochlorothiazide as usually compatible with breast-feeding.

    Children, infants, neonates, premature neonates

    Nephrocalcinosis (calcium nephrolithiasis) has occurred in some premature neonates treated with furosemide for edema. Nephrocalcinosis (calcium nephrolithiasis) has also been reported in infants and children under 4 years with no history of prematurity who are receiving chronic furosemide therapy. The concurrent use of chlorothiazide has been reported to decrease hypercalciuria and dissolve some calculi. Pediatric patients receiving furosemide therapy should have their renal function monitored and renal ultrasonography should be considered. In addition, premature neonates who receive furosemide in the first few weeks of life may have an increased risk of persistent patent ductus arteriosus. Doses exceeding 1 mg/kg/24 hours have been associated with toxicity, including ototoxicity, in premature neonates with a postconceptual age less than 31 weeks. Safety and efficacy have not been established for use of the subcutaneous furosemide on-body infusor in pediatric patients.

    Ascites, hepatic disease, hepatic encephalopathy

    Subcutaneous furosemide infusion is contraindicated in patients with certain hepatic diseases, specifically hepatic cirrhosis or ascites. The manufacturer recommends initiating furosemide therapy in the hospital with small doses and close monitoring of clinical status and electrolyte balance in patients with hepatic disease (i.e., hepatic cirrhosis) and ascites. Rapid changes in fluid and electrolyte balance may cause hepatic encephalopathy and coma in patients with hepatic cirrhosis and ascites. Furosemide therapy should not be instituted in hepatic encephalopathy (hepatic coma) or in patients with electrolyte depletion until the condition is improved. The presence of cirrhosis may also increase the potential for the development of hypokalemia in patients receiving furosemide therapy. Hypokalemia and metabolic alkalosis may be prevented with potassium supplementation and, if necessary, an aldosterone antagonist.

    Prostatic hypertrophy, urethral stricture, urinary retention

    The administration of furosemide to patients with severe symptoms of urinary retention (due to bladder emptying disorders, prostatic hypertrophy, urethral stricture) can precipitate acute urinary retention. This is related to increased production and retention of urine. Monitor these patients carefully, especially during the initiation of furosemide therapy.

    Thyroid disease

    Use high doses (more than 80 mg) of furosemide cautiously in patients with thyroid disease. At high doses, furosemide may inhibit the binding of thyroid hormones to carrier proteins, resulting in a transient increase in free thyroid hormones followed by an overall decrease in total thyroid hormone concentrations.

    Geriatric

    Greater sensitivity to the hypotensive and diuretic effects of furosemide is possible in geriatric patients. Reported clinical experience has not identified differences in responses between older adult and younger adult patients. In general, dose selection for elderly patients should be cautious, usually starting at the low end of the dosing range. Furosemide is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection and it may be useful to monitor renal function. 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. Furosemide has anticholinergic properties which may be problematic in the elderly.

    Pulmonary edema

    Subcutaneous furosemide infusion is not indicated for treatment of acute pulmonary edema or for use in emergency situations. The total dose of furosemide delivered by the subcutaneous on-body infusor is only 80 mg.

    Magnetic resonance imaging (MRI)

    The use of subcutaneous furosemide infusion via on-body infusor is not compatible for use in a magnetic resonance imaging (MRI) setting.

    ADVERSE REACTIONS

    Severe

    hepatic encephalopathy / Delayed / Incidence not known
    pancreatitis / Delayed / Incidence not known
    interstitial nephritis / Delayed / Incidence not known
    azotemia / Delayed / Incidence not known
    oliguria / Early / Incidence not known
    thrombosis / Delayed / Incidence not known
    thromboembolism / Delayed / Incidence not known
    hearing loss / Delayed / Incidence not known
    agranulocytosis / Delayed / Incidence not known
    aplastic anemia / Delayed / Incidence not known
    hemolytic anemia / Delayed / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    exfoliative dermatitis / Delayed / Incidence not known
    Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known
    toxic epidermal necrolysis / Delayed / Incidence not known
    acute generalized exanthematous pustulosis (AGEP) / Delayed / Incidence not known
    erythema multiforme / Delayed / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    vasculitis / Delayed / Incidence not known
    anaphylactic shock / Rapid / Incidence not known

    Moderate

    hypokalemia / Delayed / 38.0-38.0
    hypomagnesemia / Delayed / 12.4-12.4
    jaundice / Delayed / Incidence not known
    constipation / Delayed / Incidence not known
    elevated hepatic enzymes / Delayed / Incidence not known
    cholestasis / Delayed / Incidence not known
    blurred vision / Early / Incidence not known
    xanthopsia / Delayed / Incidence not known
    hypovolemia / Early / Incidence not known
    hypochloremia / Delayed / Incidence not known
    hyponatremia / Delayed / Incidence not known
    orthostatic hypotension / Delayed / Incidence not known
    hypocalcemia / Delayed / Incidence not known
    metabolic alkalosis / Delayed / Incidence not known
    phlebitis / Rapid / Incidence not known
    gout / Delayed / Incidence not known
    hyperuricemia / Delayed / Incidence not known
    diabetes mellitus / Delayed / Incidence not known
    hyperglycemia / Delayed / Incidence not known
    glycosuria / Early / Incidence not known
    hypercholesterolemia / Delayed / Incidence not known
    hypertriglyceridemia / Delayed / Incidence not known
    eosinophilia / Delayed / Incidence not known
    anemia / Delayed / Incidence not known
    leukopenia / Delayed / Incidence not known
    thrombocytopenia / Delayed / Incidence not known
    bullous rash / Early / Incidence not known
    bladder spasm / Early / Incidence not known
    erythema / Early / Incidence not known
    edema / Delayed / Incidence not known
    nephrolithiasis / Delayed / Incidence not known
    hypercalciuria / Delayed / Incidence not known

    Mild

    anorexia / Delayed / Incidence not known
    diarrhea / Early / Incidence not known
    nausea / Early / Incidence not known
    vomiting / Early / Incidence not known
    abdominal pain / Early / Incidence not known
    headache / Early / Incidence not known
    restlessness / Early / Incidence not known
    vertigo / Early / Incidence not known
    paresthesias / Delayed / Incidence not known
    dizziness / Early / Incidence not known
    syncope / Early / Incidence not known
    polyuria / Early / Incidence not known
    tinnitus / Delayed / Incidence not known
    fever / Early / Incidence not known
    weakness / Early / Incidence not known
    rash / Early / Incidence not known
    purpura / Delayed / Incidence not known
    photosensitivity / Delayed / Incidence not known
    pruritus / Rapid / Incidence not known
    urticaria / Rapid / Incidence not known
    muscle cramps / Delayed / Incidence not known
    application site reaction / Early / Incidence not known
    injection site reaction / Rapid / 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.
    Acetohexamide: (Minor) Furosemide may cause hyperglycemia and glycosuria in patients with diabetes mellitus. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely.
    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) Furosemide 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 furosemide 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) Furosemide may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. (Minor) Furosemide 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 furosemide 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) Furosemide 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 furosemide 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. (Minor) Furosemide 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 furosemide and all antidiabetic agents. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely.
    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.
    Amikacin: (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).
    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).
    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: (Minor) Furosemide may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. This combination should be used with caution and patients monitored for increased side effects.
    Amoxicillin; Clarithromycin; Omeprazole: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and loop diuretic use due to risk for hypomagnesemia. (Minor) Furosemide may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. This combination should be used with caution and patients monitored for increased side effects.
    Amoxicillin; Clavulanic Acid: (Minor) Furosemide may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. This combination should be used with caution and patients monitored for increased side effects.
    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.
    Ampicillin: (Minor) Furosemide may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. This combination should be used with caution and patients monitored for increased side effects.
    Ampicillin; Sulbactam: (Minor) Furosemide may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. This combination should be used with caution and patients monitored for increased side effects.
    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) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant furosemide and meloxicam use. Nonsteroidal antiinflammatory drugs (NSAIDs) may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of loop diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
    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.
    Cabozantinib: (Minor) Monitor for an increase in cabozantinib-related adverse reactions if coadministration with furosemide is necessary. Cabozantinib is a Multidrug Resistance Protein 2 (MRP2) substrate and furosemide is an MRP2 inhibitor. MRP2 inhibitors have the potential to increase plasma concentrations of cabozantinib; however, the clinical relevance of this interaction is unknown.
    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) Furosemide may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia.
    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.
    Chlophedianol; Guaifenesin; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Chloroprocaine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    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) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant furosemide and ibuprofen use. Nonsteroidal antiinflammatory drugs (NSAIDs) may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of loop diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. (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.
    Chlorpropamide: (Minor) Furosemide may cause hyperglycemia and glycosuria in patients with diabetes mellitus. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely.
    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.
    Cholestyramine: (Moderate) In a study of 6 healthy volunteers, concurrent administration of cholestyramine with oral furosemide reduced the bioavailability of furosemide by 95% and reduced the diuretic response by 77%. Concomitant administration with colestipol reduced furosemide bioavailability by 80% and the diuretic response by 58%. The manufacturer of colestipol recommends administering other drugs at least 1 hour before or at least 4-6 hours after the administration of colestipol and that the interval between the administration of colestipol and other drugs should be as long as possible.
    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: (Moderate) Closely monitor renal function and audiometric testing if concomitant use of cisplatin and furosemide is necessary. Both cisplatin and furosemide can cause nephrotoxicity and ototoxicity, which may be additive when used together.
    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.
    Colestipol: (Moderate) In a study of 6 healthy volunteers, concurrent administration of cholestyramine with oral furosemide reduced the bioavailability of furosemide by 95% and reduced the diuretic response by 77%. Concomitant administration with colestipol reduced furosemide bioavailability by 80% and the diuretic response by 58%. The manufacturer of colestipol recommends administering other drugs at least 1 hour before or at least 4-6 hours after the administration of colestipol and that the interval between the administration of colestipol and other drugs should be as long as possible.
    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.
    Cyclosporine: (Moderate) Coadministration of furosemide and cyclosporine increases the risk of gouty arthritis. This is a result of furosemide-induced hyperuricemia and the impairment of renal urate excretion by cyclosporine.
    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) Furosemide may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia.
    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) Furosemide 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. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if these drugs are initiated.
    Darifenacin: (Minor) Diuretics can increase urinary frequency, which may aggravate bladder symptoms.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Moderate) The manufacturer of dasabuvir; ombitasvir; paritaprevir; ritonavir and ombitasvir; paritaprevir; ritonavir recommends caution and clinical monitoring if administered concurrently with furosemide. Use of these drugs in combination has resulted in elevated furosemide maximum plasma concentrations (Cmax). Individualize the dose of furosemide based on the patient's clinical response. The dose should be re-adjusted after completion of the hepatitis C treatment regimen. (Moderate) The manufacturer of dasabuvir; ombitasvir; paritaprevir; ritonavir recommends caution and clinical monitoring if administered concurrently with furosemide. Use of these drugs in combination has resulted in elevated furosemide maximum plasma concentrations (Cmax). Individualize the dose of furosemide based on the patient's clinical response. The dose should be re-adjusted after completion of the 4-drug hepatitis C treatment regimen.
    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) Concomitant use of dichlorphenamide and furosemide is not recommended because of an increased risk of furosemide-related adverse effects and risk for hypokalemia. Monitor closely for signs of drug toxicity if coadministration cannot be avoided in some patients furosemide dose adjustment might be necessary. Increased furosemide exposure is possible. Dichlorphenamide inhibits OAT1. Furosemide is an OAT1 substrate. Dichlorphenamide also increases potassium excretion and can cause hypokalemia and should be used cautiously with other drugs that may cause hypokalemia including furosemide. 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) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant furosemide and diclofenac use. Nonsteroidal anti-inflammatory drugs (NSAIDs) may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of [loop/thiazide diuretics] and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
    Diclofenac; Misoprostol: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant furosemide and diclofenac use. Nonsteroidal anti-inflammatory drugs (NSAIDs) may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of [loop/thiazide diuretics] and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
    Dicloxacillin: (Minor) Furosemide may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. This combination should be used with caution and patients monitored for increased side effects.
    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) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant furosemide and ibuprofen use. Nonsteroidal antiinflammatory drugs (NSAIDs) may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of loop diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
    Diphenhydramine; Naproxen: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant furosemide and naproxen use. Nonsteroidal antiinflammatory drugs (NSAIDs) may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of loop diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
    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) Furosemide may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. (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) Furosemide may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia.
    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) Furosemide may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia.
    Ertugliflozin; Sitagliptin: (Minor) Furosemide 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. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if these drugs are initiated.
    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.
    Fosphenytoin: (Moderate) Monitor for loss of furosemide efficacy during concomitant fosphenytoin use. Fosphenytoin interferes directly with renal action of furosemide. There is evidence that treatment with fosphenytoin leads to decreased intestinal absorption of furosemide, and consequently to lower peak serum furosemide concentrations.
    General anesthetics: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Gentamicin: (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).
    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: (Minor) Furosemide may cause hyperglycemia and glycosuria in patients with diabetes mellitus. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely.
    Glimepiride; Rosiglitazone: (Minor) Furosemide 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 furosemide and all antidiabetic agents. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely. (Minor) Furosemide may cause hyperglycemia and glycosuria in patients with diabetes mellitus. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely.
    Glipizide: (Minor) Furosemide may cause hyperglycemia and glycosuria in patients with diabetes mellitus. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely.
    Glipizide; Metformin: (Minor) Furosemide may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. (Minor) Furosemide may cause hyperglycemia and glycosuria in patients with diabetes mellitus. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely.
    Glyburide: (Minor) Furosemide may cause hyperglycemia and glycosuria in patients with diabetes mellitus. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely.
    Glyburide; Metformin: (Minor) Furosemide may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. (Minor) Furosemide may cause hyperglycemia and glycosuria in patients with diabetes mellitus. 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) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant furosemide and ibuprofen use. Nonsteroidal antiinflammatory drugs (NSAIDs) may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of loop diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. (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) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant furosemide and ibuprofen use. Nonsteroidal antiinflammatory drugs (NSAIDs) may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of loop diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
    Ibuprofen; Famotidine: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant furosemide and ibuprofen use. Nonsteroidal antiinflammatory drugs (NSAIDs) may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of loop diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
    Ibuprofen; Oxycodone: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant furosemide and ibuprofen use. Nonsteroidal antiinflammatory drugs (NSAIDs) may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of loop diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. (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) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant furosemide and ibuprofen use. Nonsteroidal antiinflammatory drugs (NSAIDs) may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of loop diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. (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.
    Kanamycin: (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).
    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) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant furosemide and ketorolac use. Nonsteroidal antiinflammatory drugs (NSAIDs) may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of loop diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
    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. (Minor) Furosemide may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. This combination should be used with caution and patients monitored for increased side effects.
    Lansoprazole; Naproxen: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant furosemide and naproxen use. Nonsteroidal antiinflammatory drugs (NSAIDs) may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of loop diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. (Moderate) Monitor magnesium concentration before and periodically during concomitant lansoprazole and loop diuretic use due to risk for hypomagnesemia.
    Leflunomide: (Moderate) Closely monitor for furosemide-induced side effects such as excessive fluid loss or hypotension when these drugs are used together. In some patients, a dosage reduction of furosemide may be required. Following oral administration, leflunomide is metabolized to an active metabolite, teriflunomide, which is responsible for essentially all of leflunomide's in vivo activity. Teriflunomide is an inhibitor of the renal uptake organic anion transporter OAT3. Use of teriflunomide with furosemide, a substrate of OAT3, may increase furosemide plasma concentrations.
    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.
    Levothyroxine: (Moderate) Use high doses (more than 80 mg) of furosemide and thyroid hormones together with caution. High doses of furosemide may inhibit the binding of thyroid hormones to carrier proteins, resulting in a transient increase in free thyroid hormones followed by an overall decrease in total thyroid hormone concentrations.
    Levothyroxine; Liothyronine (Porcine): (Moderate) Use high doses (more than 80 mg) of furosemide and thyroid hormones together with caution. High doses of furosemide may inhibit the binding of thyroid hormones to carrier proteins, resulting in a transient increase in free thyroid hormones followed by an overall decrease in total thyroid hormone concentrations.
    Levothyroxine; Liothyronine (Synthetic): (Moderate) Use high doses (more than 80 mg) of furosemide and thyroid hormones together with caution. High doses of furosemide may inhibit the binding of thyroid hormones to carrier proteins, resulting in a transient increase in free thyroid hormones followed by an overall decrease in total thyroid hormone concentrations.
    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) Furosemide may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. (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.
    Liothyronine: (Moderate) Use high doses (more than 80 mg) of furosemide and thyroid hormones together with caution. High doses of furosemide may inhibit the binding of thyroid hormones to carrier proteins, resulting in a transient increase in free thyroid hormones followed by an overall decrease in total thyroid hormone concentrations.
    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.
    Maraviroc: (Moderate) Use caution and closely monitor for increased adverse effects during concurrent administration of maraviroc and furosemide as increased maraviroc concentrations may occur. Maraviroc is a substrate of multidrug resistance-associated protein (MRP2); furosemide is an inhibitor of MRP2. The effects of this transporter on the concentrations of maraviroc are unknown, although an increase in concentrations and thus, toxicity, are possible.
    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) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant furosemide and meloxicam use. Nonsteroidal antiinflammatory drugs (NSAIDs) may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of loop diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
    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) Furosemide may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia.
    Metformin; Repaglinide: (Minor) Furosemide may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. (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) Furosemide may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. (Minor) Furosemide 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 furosemide and all antidiabetic agents. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely.
    Metformin; Saxagliptin: (Minor) Furosemide may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. (Minor) Furosemide 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. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if these drugs are initiated.
    Metformin; Sitagliptin: (Minor) Furosemide may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. (Minor) Furosemide 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. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if these drugs are initiated.
    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.
    Methotrexate: (Moderate) Furosemide undergoes significant renal tubular secretion. Concomitant administration of furosemide with other drugs that undergo significant renal tubular secretion, such as methotrexate, may result in decreased effect of furosemide and, conversely, decreased elimination of the other drug. High dose treatment of both furosemide and other drugs that undergo renal tubular secretion may result in increased toxicity of both drugs.
    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.
    Nafcillin: (Minor) Furosemide may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. This combination should be used with caution and patients monitored for increased side effects.
    Naproxen: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant furosemide and naproxen use. Nonsteroidal antiinflammatory drugs (NSAIDs) may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of loop diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
    Naproxen; Esomeprazole: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant furosemide and naproxen use. Nonsteroidal antiinflammatory drugs (NSAIDs) may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of loop diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. (Moderate) Monitor magnesium concentration before and periodically during concomitant esomeprazole and loop diuretic use due to risk for hypomagnesemia.
    Naproxen; Pseudoephedrine: (Moderate) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant furosemide and naproxen use. Nonsteroidal antiinflammatory drugs (NSAIDs) may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of loop diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics. (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.
    Nitisinone: (Moderate) Monitor for increased furosemide-related adverse effects including excessive fluid loss or hypotension if coadministered with nitisinone. Increased furosemide exposure is possible. Nitisinone inhibits OAT3. Furosemide is an OAT3 substrate. When coadministered, the AUC of furosemide increased by 72% and Cmax increased by 12%.
    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.
    Ombitasvir; Paritaprevir; Ritonavir: (Moderate) The manufacturer of dasabuvir; ombitasvir; paritaprevir; ritonavir and ombitasvir; paritaprevir; ritonavir recommends caution and clinical monitoring if administered concurrently with furosemide. Use of these drugs in combination has resulted in elevated furosemide maximum plasma concentrations (Cmax). Individualize the dose of furosemide based on the patient's clinical response. The dose should be re-adjusted after completion of the hepatitis C treatment regimen.
    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. (Minor) Furosemide may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. This combination should be used with caution and patients monitored for increased side effects.
    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.
    Oxacillin: (Minor) Furosemide may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. This combination should be used with caution and patients monitored for increased side effects.
    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.
    Paromomycin: (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).
    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.
    Penicillin G Benzathine: (Minor) Furosemide may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. This combination should be used with caution and patients monitored for increased side effects.
    Penicillin G Benzathine; Penicillin G Procaine: (Minor) Furosemide may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. This combination should be used with caution and patients monitored for increased side effects.
    Penicillin G Procaine: (Minor) Furosemide may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. This combination should be used with caution and patients monitored for increased side effects.
    Penicillin G: (Minor) Furosemide may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. This combination should be used with caution and patients monitored for increased side effects.
    Penicillin V: (Minor) Furosemide may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. This combination should be used with caution and patients monitored for increased side effects.
    Penicillins: (Minor) Furosemide may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. This combination should be used with caution and patients monitored for increased side effects.
    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.
    Phenytoin: (Moderate) Monitor for loss of furosemide efficacy during concomitant phenytoin use. Phenytoin interferes directly with renal action of furosemide. There is evidence that treatment with phenytoin leads to decreased intestinal absorption of furosemide, and consequently to lower peak serum furosemide concentrations.
    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) Furosemide 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 furosemide and all antidiabetic agents. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely.
    Pioglitazone; Glimepiride: (Minor) Furosemide 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 furosemide and all antidiabetic agents. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely. (Minor) Furosemide may cause hyperglycemia and glycosuria in patients with diabetes mellitus. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely.
    Pioglitazone; Metformin: (Minor) Furosemide may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. (Minor) Furosemide 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 furosemide and all antidiabetic agents. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely.
    Piperacillin: (Minor) Furosemide may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. This combination should be used with caution and patients monitored for increased side effects.
    Piperacillin; Tazobactam: (Minor) Furosemide may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. This combination should be used with caution and patients monitored for increased side effects.
    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.
    Plazomicin: (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).
    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.
    Porfimer: (Major) Avoid coadministration of porfimer with furosemide due to the risk of increased photosensitivity. All patients treated with porfimer will be photosensitive. Concomitant use of other photosensitizing agents like furosemide may increase the risk of a photosensitivity reaction.
    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 furosemide. Furosemide 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 furosemide. Furosemide 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 may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly. Furthermore, two of four placebo-controlled trials showed that elderly patients with dementia-related psychosis receiving the combination of risperidone and furosemide had a higher incidence of mortality than those receiving either agent alone. The mechanism for this adverse association is unknown. Caution should be exercised when the combined use of risperidone and furosemide is necessary in those with dementia-related psychosis.
    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) Furosemide 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 furosemide 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) Furosemide 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. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if these drugs are initiated.
    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) Furosemide 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. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if these drugs are initiated.
    Sitagliptin: (Minor) Furosemide 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. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if these drugs are initiated.
    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.
    Streptomycin: (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).
    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.
    Sucralfate: (Moderate) Separate the administration of oral furosemide and sucralfate by at least 2 hours. Simultaneous coadministration may reduce furosemide efficacy.
    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) Furosemide may cause hyperglycemia and glycosuria in patients with diabetes mellitus. 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) Monitor blood pressure as well as for signs of worsening renal function and loss of diuretic efficacy, including antihypertensive effects, during concomitant furosemide and naproxen use. Nonsteroidal antiinflammatory drugs (NSAIDs) may cause a dose-dependent reduction in renal blood flow, which may precipitate overt renal decompensation, and concomitant diuretic use increases the risk of this reaction. NSAIDs have been shown to reduce the natriuretic effect of loop diuretics and are associated with fluid retention which may blunt the cardiovascular effects of diuretics.
    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.
    Teriflunomide: (Moderate) Teriflunomide is an inhibitor of the renal uptake organic anion transporter OAT3. Use of teriflunomide with furosemide, a substrate of OAT3, may increase furosemide plasma concentrations. Monitor for increased adverse effects from furosemide, such as excessive fluid loss or hypotension.
    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) Furosemide 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 furosemide 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.
    Thyroid hormones: (Moderate) Use high doses (more than 80 mg) of furosemide and thyroid hormones together with caution. High doses of furosemide may inhibit the binding of thyroid hormones to carrier proteins, resulting in a transient increase in free thyroid hormones followed by an overall decrease in total thyroid hormone concentrations.
    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.
    Tobramycin: (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).
    Tolazamide: (Minor) Furosemide may cause hyperglycemia and glycosuria in patients with diabetes mellitus. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely.
    Tolbutamide: (Minor) Furosemide may cause hyperglycemia and glycosuria in patients with diabetes mellitus. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely.
    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 furosemide 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.
    Vancomycin: (Moderate) Vancomycin should be used cautiously with other ototoxic drugs such as furosemide.
    Vasopressin, ADH: (Minor) Use of furosemide with vasopressin increases the effect of vasopressin on osmolar clearance and urine flow. Furosemide increases osmolar clearance 4-fold and urine flow 9-fold when coadministered with exogenous vasopressin in healthy subjects.
    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.
    Verteporfin: (Moderate) Use caution if coadministration of verteporfin with furosemide is necessary due to the risk of increased photosensitivity. Verteporfin is a light-activated drug used in photodynamic therapy; all patients treated with verteporfin will be photosensitive. Concomitant use of other photosensitizing agents like furosemide may increase the risk of a photosensitivity reaction.
    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.
    Vonoprazan; Amoxicillin: (Minor) Furosemide may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. This combination should be used with caution and patients monitored for increased side effects.
    Vonoprazan; Amoxicillin; Clarithromycin: (Minor) Furosemide may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. This combination should be used with caution and patients monitored for increased side effects.
    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

    Published data from observational studies, case reports, and postmarketing reports have not demonstrated a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes with furosemide use during pregnancy according to the parenteral furosemide product label. However, the oral furosemide product label includes a recommendation to avoid furosemide use during pregnancy unless the potential benefit justifies the potential risk to the fetus. Due to the risk for higher birth weights, monitor fetal growth with furosemide therapy during pregnancy. Furosemide has been shown to cause unexplained maternal deaths and abortions in rabbits at 2, 4, and 8 times the maximum recommended human dose. Data from these studies involving rabbits indicate that fetal lethality may precede maternal deaths. In studies involving pregnant mice and rabbits, an increased incidence and severity of hydronephrosis (distension of the renal pelvis and, in some cases, ureters) was observed in fetuses exposed to furosemide during pregnancy compared fetuses not exposed to furosemide.[28429]

    Use caution when administering furosemide to a breast-feeding mother. Furosemide is excreted in human breast milk. In addition, furosemide may suppress lactation as a result of intense diuresis. Previous American Academy of Pediatrics (AAP) recommendations considered chlorthalidone, chlorothiazide, and hydrochlorothiazide as usually compatible with breast-feeding.

    MECHANISM OF ACTION

    Furosemide 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. The manufacturer also states that furosemide inhibits the absorption of sodium and chloride in the proximal and distal tubules. A profound diuresis results from the increased urinary excretion of sodium, chloride, potassium, and hydrogen ions. In addition, furosemide increases the excretion of calcium, magnesium, bicarbonate, ammonium, and phosphate. The diuresis caused by furosemide 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.
     
    Furosemide's effectiveness is independent of the acid-base status of the patient. Renal vasodilation occurs following administration of furosemide; renal vascular resistance decreases, and renal blood flow is enhanced. Reduced peripheral vascular resistance and increased peripheral venous capacitance also occur, and the subsequent decrease in left ventricular filling pressure may contribute to the drug's beneficial effect in patients with congestive heart failure. Initially, diuretics lower blood pressure by causing hypovolemia (decreased plasma and extracellular fluid), a temporary increase in glomerular filtration rate, and a decreased cardiac output. Cardiac output eventually returns to normal, but peripheral resistance is now reduced, resulting in lower blood pressure. In general, diuretics worsen glucose tolerance. In addition, loop diuretics have been associated with hypercholesterolemia and hypertriglyceridemia.

    PHARMACOKINETICS

    Furosemide is administered orally, intravenously, and subcutaneously. It is 91% to 99% plasma protein-bound, mainly to albumin. Furosemide undergoes minimal metabolism in the liver, with 50% to 80% of a dose excreted in the urine within 24 hours; significantly more furosemide is excreted in the urine after IV administration as compared to oral. The remainder of the drug is eliminated through nonrenal mechanisms including excretion in the feces. In patients with significant renal impairment, nonrenal elimination can increase to 98%. The half-life of furosemide is approximately 2 hours.
     
    Affected cytochrome P450 isoenzymes: none

    Oral Route

    Furosemide is absorbed erratically after an oral dose, and food will delay this absorption but will not alter the diuretic response. The bioavailability of the tablet and solution in healthy fasted volunteers is 64% and 60%, respectively. Although furosemide solution is more rapidly absorbed compared to the tablet, peak plasma concentrations and the AUC are not significantly different between the 2 dosage forms. Diuresis generally begins 30 to 60 minutes after oral administration, with the peak effect occurring within 1 to 2 hours. The duration of diuresis is 6 to 8 hours.

    Intravenous Route

    Diuresis generally begins about 5 minutes after IV administration of furosemide. The peak effect occurs within the first 30 minutes and the duration is approximately 2 hours.

    Intramuscular Route

    Onset of action begins approximately 30 minutes after IM administration and persists for approximately 4 to 8 hours.[64934]

    Subcutaneous Route

    In patients with NYHA Class II and Class III heart failure, diuresis and natriuresis were similar between subcutaneous furosemide infusion (30 mg infused over 1 hr, followed by 12.5 mg per hour for 4 hours (total dose: 80 mg)) and intravenous furosemide (two 40 mg bolus doses separated by 120 minutes) at 8 and 24 hours post-dose. Following dose initiation, typical therapeutic levels were reached within 30 minutes and maintained for up to 6 hours, while the diuretic effect duration of subcutaneous furosemide is up to 8 hours or more. Median Tmax was 4 hours for subcutaneous furosemide compared to approximately 2 hours for intravenous furosemide. Cmax of subcutaneous furosemide infusion is 2,040 +/- 449 nanograms/mL compared to 8,580 +/- 2,540 nanograms/mL for furosemide intermittent intravenous bolus doses. The AUC and half-life of subcutaneous furosemide infusion are 13,000 +/- 4,000 nanograms x hour/mL and 3.2 hours, respectively, compared 13,000 +/- 4,050 nanograms x hour/mL and 2.6 hours, respectively, with intermittent intravenous furosemide bolus doses.