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  • CLASSES

    Loop Diuretics

    DEA CLASS

    Rx

    DESCRIPTION

    Potent parenteral and oral loop diuretic; useful in patients who are unresponsive to other diuretics; greater risk of ototoxicity when compared to other loop diuretics.

    COMMON BRAND NAMES

    Edecrin

    HOW SUPPLIED

    Edecrin/Ethacrynate Sodium/Ethacrynic Acid Intravenous Inj Pwd F/Sol: 50mg
    Edecrin/Ethacrynic Acid Oral Tab: 25mg

    DOSAGE & INDICATIONS

    For the treatment of peripheral edema, including idiopathic edema, lymphedema, or edema secondary to ascites, heart failure, or nephrotic syndrome.
    Oral dosage
    Adults

    Initially, 50 to 100 mg PO per day, usually given once or twice daily. May increase by 25 to 50 mg/day to achieve clinical goals. Maximum dosage is 200 mg PO twice daily (400 mg/day PO). Geriatric patients may be more sensitive to the effects of the usual adult dosage.

    Children and Adolescents

    Initially, 1 mg/kg PO once daily. May increase up to 3 mg/kg/day PO. Adjust dosage at intervals of 2 to 3 days.

    Intravenous dosage (ethacrynate sodium)
    Adults

    Initially, 50 mg or 0.5 to 1 mg/kg IV injected slowly (over several minutes); then may repeat after 2 to 4 hours at a new injection site. Single IV doses more than 100 mg are not recommended. Geriatric patients may be more sensitive to the effects of the usual adult dosage.

    Children† and Adolescents†

    Initially, 1 mg/kg IV once daily. Repeat doses are not routinely recommended, but can be given every 8 to 12 hours if needed.

    For the treatment of acute pulmonary edema.
    Intravenous dosage (ethacrynate sodium)
    Adults

    Initially, 50 mg or 0.5 to 1 mg/kg IV injected slowly (over several minutes); dose may be repeated, at a new injection site, in 1 hour if needed. Geriatric patients may be more sensitive to the effects of the usual adult dosage.

    Children† and Adolescents†

    Initially, 1 mg/kg IV once daily. Repeat doses are not routinely recommended, but can be given every 8 to 12 hours if needed.

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

    Single doses of 20—40 mg IV can be administered every 1—2 hours in combination with IV saline. Saline administration should begin before the first dose of ethacrynic acid is administered to avoid volume contraction which may limit calciuria.

    Geriatric

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

    For the treatment of hypertension†.
    Oral dosage
    Adults

    Initially, 25—50 mg PO daily. May increase gradually up to 100 mg/day PO, given in 2 divided doses. Doses up to 200 mg PO twice daily have been used in patients with renal insufficiency.

    Geriatric

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

    Children

    Initially, 25 mg PO daily, then increase by 25 mg/day if needed.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    400 mg/day PO or 100 mg/dose IV.

    Geriatric

    400 mg/day PO or 100 mg/dose IV.

    Adolescents

    3 mg/kg/day PO; safety and efficacy of IV administration has not been established but 1 mg/kg/dose IV has been used.

    Children

    3 mg/kg/day PO; safety and efficacy of IV administration has not been established but 1 mg/kg/dose IV has been used.

    Infants

    Use is contraindicated.

    DOSING CONSIDERATIONS

    Hepatic Impairment

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

    Renal Impairment

    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 after meals.

    Injectable Administration

    Do not administer subcutaneously or IM because of local pain and irritation.

    Intravenous Administration

    Reconstitution:
    Reconstitute vial containing ethacrynate sodium equivalent to 50 mg of ethacrynic acid by adding 50 mL of 5% Dextrose injection or 0.9% Sodium Chloride injection. The resulting IV solution contains the equivalent of 1 mg/mL of ethacrynic acid. If 5% Dextrose injection with a pH <= 5 is used, a hazy or opalescent solution may develop and should not be used.
     
    Intravenous injection:
    Infuse slowly IV over 20—30 minutes through the tubing of a freely running IV infusion or inject directly over several minutes.

    STORAGE

    Edecrin:
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Ethacrynic acid is contraindicated for patients with known hypersensitivity to any component of the product. In contrast to other loop diuretics, ethacrynic acid lacks a sulfonamide substituent. Although cross-sensitivity among sulfonamide-derived loop diuretics is rare, ethacrynic acid has been used as an alternative diuretic in patients with documented severe allergy to loop diuretics such as bumetanide, furosemide, or torsemide.

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

    Preexisting electrolyte imbalance, including conditions of hyponatremia, hypokalemia, hypocalcemia, hypochloremia, and hypomagnesemia, should be corrected prior to initiation of ethacrynic acid therapy. Further, use is counter-intuitive in patients with preexisting dehydration. Ethacrynic acid is a potent diuretic which, if given in excessive amounts, may lead to profound diuresis with water and electrolyte depletion (dehydration and electrolyte imbalance). Therefore, careful medical supervision is required, and dose and dose schedule must be adjusted to the individual patient's needs. Loop diuretics may induce metabolic alkalosis associated with hypokalemia and hypochloremia; this acid/base imbalance is effectively treated with potassium chloride replacement.

    Hepatic disease, hepatic encephalopathy

    Ethacrynic acid can produce marked fluid and electrolyte shifts and can precipitate serious hepatic effects in susceptible patients. Therefore, ethacrynic acid should be used with caution in patients with hepatic disease such as cirrhosis or hepatic encephalopathy.

    Diarrhea

    Ethacrynic acid therapy is contraindicated in patients with a history of ethacrynic acid-induced severe, watery diarrhea. Further, use with caution in patients with preexisting diarrhea as such therapy may worsen this condition and result in additive hypokalemia.

    Hypotension, hypovolemia, orthostatic hypotension, sympathectomy, syncope

    Patients with pre-existing hypovolemia or hypotension should have their condition corrected before ethacrynic acid is initiated. Use this medication with caution in patients with a history of orthostatic hypotension and/or syncope as orthostatic hypotension may occur during treatment with loop diuretics and 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. Greater sensitivity to the hypotensive and diuretic effects of ethacrynic acid is possible in older patients.

    Diabetes mellitus, hyperglycemia

    Blood and urine glucose levels should be assessed in patients with diabetes mellitus or hyperglycemia during treatment with ethacrynic acid; loop diuretics can impair glucose tolerance.

    Anuria, renal disease, renal failure, renal impairment

    Ethacrynic acid use is contraindicated in patients with anuria. It should be used cautiously in any patient with renal disease such as severe renal impairment or renal failure. Drug-induced hypovolemia can precipitate azotemia in these patients. If increasing azotemia, and/ or oliguria occur during treatment of severe, progressive renal disease, the ethacrynic acid should be discontinued. Ethacrynic acid 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. Ethacrynic acid may be less effective in these patients and delayed excretion of drug may increase the risk of toxicity.

    Systemic lupus erythematosus (SLE)

    Use with caution in patients with a history of systemic lupus erythematosus (SLE) as ethacrynic acid has been reported to activate or exacerbate SLE.

    Gout, hyperuricemia

    Loop diuretics, such as ethacrynic acid, can cause hyperuricemia. Ethacrynic acid is relatively contraindicated in patients with gout or preexisting hyperuricemia.

    Acute myocardial infarction

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

    Heart failure, hyperaldosteronism, ventricular arrhythmias

    Patients with ventricular arrhythmias, heart failure, potassium-losing nephropathy, or hyperaldosteronism (aldosterone excess) should be monitored closely since ethacrynic acid-induced hypokalemia can exacerbate these conditions.

    Pancreatitis

    Use ethacrynic acid with caution in patients with a history of pancreatitis as such therapy has been reported to cause pancreatitis in a small number of patients.

    Children, infants, neonates

    Safe and effective use of ethacrynic acid has not been established in children. Ethacrynic acid is contraindicated in infants and neonates.

    Pregnancy

    Ethacrynic acid is classified as FDA pregnancy risk category B. There are no adequate studies available on the safety of ethacrynic acid therapy during pregnancy, so the drug should be administered to pregnant women only when absolutely necessary. Diuretics are generally not recommended for the treatment of pregnancy-induced hypertension (preeclampsia, eclampsia) since they do not alter the course of toxemia and may exacerbate maternal hypovolemia associated with this condition.

    Breast-feeding

    According to the manufacturer, it is not known whether ethacrynic acid is excreted in human milk. The manufacturer recommends that a decision be made either to discontinue breast-feeding or to discontinue the drug, taking into account the importance of the drug to the mother. Diuretics, such as ethacrynic acid, may suppress lactation as a result of intense diuresis. Of note, the use of bendroflumethiazide, chlorthalidone, chlorothiazide, and hydrochlorothiazide is considered to be usually compatible with breast-feeding by the American Academy of Pediatrics (AAP) due to lack of noted adverse effects on the nursing infant. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    Geriatric

    Greater sensitivity to the hypotensive and diuretic effects of ethacrynic acid is possible for geriatric and debilitated patients, although, in general, clinical experience and clinical trials have not identified significant differences in responses between older adult and younger adult patients. In geriatric cardiac patients, rapid contraction of plasma volume and the resultant hemoconcentration should be avoided to prevent the development of thromboembolic episodes, such as cerebral vascular thromboses and pulmonary emboli which may be fatal. 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. Monitor renal function, fluid status, and electrolytes closely. 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. According to the OBRA guidelines, 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. There are many drug interactions that can potentiate the effects of antihypertensives.

    Hearing impairment

    High doses and accumulation of ethacrynic acid may cause ototoxicity. Ethacrynic acid should be used with caution in patients with preexisting hearing impairment.

    ADVERSE REACTIONS

    Severe

    agranulocytosis / Delayed / 0-1.0
    pancreatitis / Delayed / 0-1.0
    hearing loss / Delayed / Incidence not known
    GI bleeding / Delayed / Incidence not known
    azotemia / Delayed / Incidence not known
    oliguria / Early / Incidence not known

    Moderate

    neutropenia / Delayed / 0-1.0
    thrombocytopenia / Delayed / 0-1.0
    jaundice / Delayed / 0-1.0
    elevated hepatic enzymes / Delayed / 0-1.0
    confusion / Early / Incidence not known
    hypomagnesemia / Delayed / Incidence not known
    hypokalemia / Delayed / Incidence not known
    metabolic alkalosis / Delayed / Incidence not known
    hypochloremia / Delayed / Incidence not known
    hypovolemia / Early / Incidence not known
    hyponatremia / Delayed / Incidence not known
    hypocalcemia / Delayed / Incidence not known
    orthostatic hypotension / Delayed / Incidence not known
    hyperuricemia / Delayed / Incidence not known
    blurred vision / Early / Incidence not known
    hyperglycemia / Delayed / Incidence not known
    dysphagia / Delayed / Incidence not known
    hematuria / Delayed / Incidence not known

    Mild

    injection site reaction / Rapid / 1.0-10.0
    fatigue / Early / Incidence not known
    headache / Early / Incidence not known
    anxiety / Delayed / Incidence not known
    muscle cramps / Delayed / Incidence not known
    polyuria / Early / Incidence not known
    paresthesias / Delayed / Incidence not known
    syncope / Early / Incidence not known
    tinnitus / Delayed / Incidence not known
    vertigo / Early / Incidence not known
    diarrhea / Early / Incidence not known
    anorexia / Delayed / Incidence not known
    malaise / Early / Incidence not known
    vomiting / Early / Incidence not known
    nausea / Early / Incidence not known
    chills / Rapid / Incidence not known
    rash (unspecified) / Early / Incidence not known
    fever / Early / 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; Phenyltoloxamine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Acetaminophen; 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; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Acetazolamide: (Moderate) Carbonic anhydrase inhibitors promote electrolyte excretion including hydrogen ions, sodium, and potassium. They can enhance the sodium depleting effects of other diuretics when used concurrently. Pre-existing hypokalemia and hyperuricemia can also be potentiated by carbonic anhydrase inhibitors. Monitor serum potassium to determine the need for potassium supplementation and alteration in drug therapy.
    Acrivastine; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Albiglutide: (Minor) Loop diuretics, such as bumetanide, furosemide, and torsemide, may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between these drugs and all antidiabetic agents, including incretin mimetics. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if these drugs are initiated.
    Alemtuzumab: (Moderate) Alemtuzumab may cause hypotension. Careful monitoring of blood pressure and hypotensive symptoms is recommended especially in patients with ischemic heart disease and in patients on antihypertensive agents.
    Alendronate: (Moderate) When the intravenous formulation of alendronate is used for the treatment of hypercalcemia of malignancy, combination therapy with loop diuretics should be used with caution in order to avoid hypocalcemia. In patients with hypercalcemia of malignancy, the initial treatment typically includes the use of loop diuretics, in combination with saline hydration, however, diuretic therapy should not be employed prior to correction of hypovolemia and dehydration.
    Alendronate; Cholecalciferol: (Moderate) When the intravenous formulation of alendronate is used for the treatment of hypercalcemia of malignancy, combination therapy with loop diuretics should be used with caution in order to avoid hypocalcemia. In patients with hypercalcemia of malignancy, the initial treatment typically includes the use of loop diuretics, in combination with saline hydration, however, diuretic therapy should not be employed prior to correction of hypovolemia and dehydration.
    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) Concomitant use of a thiazide diuretiic, or the related drug metolazone, with a loop diuretic can cause additive electrolyte and fluid loss. In patients with creatinine clearances > 30 ml/min, the combinations may also lead to profound fluid and electrolyte loss in some patients. Thus, use cautiously and with monitoring of renal function, blood pressure, cardiac status, electrolytes (especially potassium), and monitor the clinical response for the condition treated.
    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) Concomitant use of a thiazide diuretiic, or the related drug metolazone, with a loop diuretic can cause additive electrolyte and fluid loss. In patients with creatinine clearances > 30 ml/min, the combinations may also lead to profound fluid and electrolyte loss in some patients. Thus, use cautiously and with monitoring of renal function, blood pressure, cardiac status, electrolytes (especially potassium), and monitor the clinical response for the condition treated.
    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) Ethacrynic acid 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 ethacrynic acid 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: (Moderate) Loop diuretics can decrease the hypoglycemic effects of antidiabetic agents by producing an increase in blood glucose concentrations.Patients receiving antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. (Minor) Ethacrynic acid 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 ethacrynic acid 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: (Moderate) Loop diuretics can decrease the hypoglycemic effects of antidiabetic agents by producing an increase in blood glucose concentrations. Patients receiving antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. (Minor) Ethacrynic acid 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 ethacrynic acid and all antidiabetic agents, including alogliptin. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if this drug is initiated.
    Alpha-glucosidase Inhibitors: (Minor) Loop diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely.
    Alprostadil: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as loop diuretics, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
    Aluminum Hydroxide; Magnesium Hydroxide: (Moderate) 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.
    Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (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.
    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) Concomitant use of a thiazide diuretiic, or the related drug metolazone, with a loop diuretic can cause additive electrolyte and fluid loss. In patients with creatinine clearances > 30 ml/min, the combinations may also lead to profound fluid and electrolyte loss in some patients. Thus, use cautiously and with monitoring of renal function, blood pressure, cardiac status, electrolytes (especially potassium), and monitor the clinical response for the condition treated.
    Aminoglycosides: (Moderate) The risk of ototoxicity or nephrotoxicity secondary to aminoglycosides may be increased by the addition of concomitant therapies with similar side effects, including loop diuretics. If loop diuretics and aminoglycosides are used together, it would be prudent to monitor renal function parameters, serum electrolytes, and serum aminoglycoside concentrations during therapy. Audiologic monitoring may be advisable during high dose therapy or therapy of long duration, when hearing loss is suspected, or in selected risk groups (e.g., neonates).
    Amiodarone: (Major) Monitor serum electrolytes if coadministration of ethacrynic acid and amiodarone is necessary. Ethacrynic acid therapy may cause electrolyte abnormalities (i.e., hypokalemia, hypomagnesemia) which may exaggerate the degree of QTc prolongation and increase the potential for torsade de pointes.
    Amlodipine; Benazepril: (Moderate) Coadministration of loop diuretics and Angiotensin-converting enzyme inhibitors (ACE inhibitors) 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; Hydrochlorothiazide, HCTZ; 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. (Moderate) Concomitant use of a thiazide diuretiic, or the related drug metolazone, with a loop diuretic can cause additive electrolyte and fluid loss. In patients with creatinine clearances > 30 ml/min, the combinations may also lead to profound fluid and electrolyte loss in some patients. Thus, use cautiously and with monitoring of renal function, blood pressure, cardiac status, electrolytes (especially potassium), and monitor the clinical response for the condition treated.
    Amlodipine; Hydrochlorothiazide, HCTZ; 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. (Moderate) Concomitant use of a thiazide diuretiic, or the related drug metolazone, with a loop diuretic can cause additive electrolyte and fluid loss. In patients with creatinine clearances > 30 ml/min, the combinations may also lead to profound fluid and electrolyte loss in some patients. Thus, use cautiously and with monitoring of renal function, blood pressure, cardiac status, electrolytes (especially potassium), and monitor the clinical response for the condition treated.
    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; 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.
    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.
    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) Ethacrynic acid 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; Lansoprazole: (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. (Minor) Ethacrynic acid 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) 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. (Minor) Ethacrynic acid 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) Ethacrynic acid 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: (Major) 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 or the selection of alternative therapeutic agents may be needed.
    Amphetamine; Dextroamphetamine Salts: (Major) 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 or the selection of alternative therapeutic agents may be needed.
    Amphetamine; Dextroamphetamine: (Major) 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 or the selection of alternative therapeutic agents may be needed.
    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) Ethacrynic acid 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) Ethacrynic acid 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) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. 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.
    Angiotensin-converting enzyme inhibitors: (Moderate) Coadministration of loop diuretics and Angiotensin-converting enzyme inhibitors (ACE inhibitors) 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) Patients receiving apomorphine may experience orthostatic hypotension, hypotension, and/or syncope. Extreme caution should be exercised if apomorphine is used concurrently with antihypertensive agents, or vasodilators such as nitrates.
    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: (Major) Because electrolyte abnormalities increase the risk of QT interval prolongation and serious arrhythmias, avoid the concomitant use of arsenic trioxide with drugs that may cause electrolyte abnormalities, particularly hypokalemia and hypomagnesemia. Examples of drugs that may cause electrolyte abnormalities includes loop diuretics. If concomitant drug use is unavoidable, frequently monitor serum electrolytes (and replace as necessary) and electrocardiograms.
    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; Omeprazole: (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.
    Atenolol; Chlorthalidone: (Moderate) Concomitant use of a thiazide diuretiic, or the related drug metolazone, with a loop diuretic can cause additive electrolyte and fluid loss. In patients with creatinine clearances > 30 ml/min, the combinations may also lead to profound fluid and electrolyte loss in some patients. Thus, use cautiously and with monitoring of renal function, blood pressure, cardiac status, electrolytes (especially potassium), and monitor the clinical response for the condition treated.
    Atracurium: (Moderate) Furosemide-induced hypokalemia can potentiate neuromuscular blockade with nondepolarizing neuromuscular blockers. In addition, furosemide may antagonize the skeletal muscle relaxing effect of tubocurarine and can potentiate neuromuscular blockade following succinylcholine administration.
    Azelaic Acid; Copper; Folic Acid; Nicotinamide; Pyridoxine; Zinc: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. (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.
    Azelastine; Fluticasone: (Moderate) Corticosteroids may accentuate the electrolyte loss associated with diuretic therapy resulting in hypokalemia and/or hypomagnesemia. While glucocorticoids with mineralocorticoid activity (e.g., cortisone, hydrocortisone) can cause sodium and fluid retention. Close monitoring of electrolytes should occur in patients receiving these drugs concomitantly.
    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) Concomitant use of a thiazide diuretiic, or the related drug metolazone, with a loop diuretic can cause additive electrolyte and fluid loss. In patients with creatinine clearances > 30 ml/min, the combinations may also lead to profound fluid and electrolyte loss in some patients. Thus, use cautiously and with monitoring of renal function, blood pressure, cardiac status, electrolytes (especially potassium), and monitor the clinical response for the condition treated.
    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; 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) Corticosteroids may accentuate the electrolyte loss associated with diuretic therapy resulting in hypokalemia and/or hypomagnesemia. While glucocorticoids with mineralocorticoid activity (e.g., cortisone, hydrocortisone) can cause sodium and fluid retention. Close monitoring of electrolytes should occur in patients receiving these drugs concomitantly.
    Benazepril: (Moderate) Coadministration of loop diuretics and Angiotensin-converting enzyme inhibitors (ACE inhibitors) 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.
    Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Coadministration of loop diuretics and Angiotensin-converting enzyme inhibitors (ACE inhibitors) 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) Concomitant use of a thiazide diuretiic, or the related drug metolazone, with a loop diuretic can cause additive electrolyte and fluid loss. In patients with creatinine clearances > 30 ml/min, the combinations may also lead to profound fluid and electrolyte loss in some patients. Thus, use cautiously and with monitoring of renal function, blood pressure, cardiac status, electrolytes (especially potassium), and monitor the clinical response for the condition treated.
    Bendroflumethiazide; Nadolol: (Moderate) Concomitant use of a thiazide diuretiic, or the related drug metolazone, with a loop diuretic can cause additive electrolyte and fluid loss. In patients with creatinine clearances > 30 ml/min, the combinations may also lead to profound fluid and electrolyte loss in some patients. Thus, use cautiously and with monitoring of renal function, blood pressure, cardiac status, electrolytes (especially potassium), and monitor the clinical response for the condition treated.
    Benzphetamine: (Major) Benzphetamine can increase both systolic and diastolic blood pressure and may counteract the activity of loop diuretics. This represents a pharmacodynamic, and not a pharmacokinetic, interaction. Close monitoring of blood pressure, especially in patients who are taking antihypertensive agents, may be needed.
    Beta-agonists: (Moderate) Loop diuretics may potentiate hypokalemia and ECG changes seen with beta agonists. Hypokalemia due to beta agonists appears to be dose related and is more likely with high dose therapy. Caution is advised when loop diuretics are coadministered with high doses of beta agonists; potassium levels may need to be monitored.
    Betamethasone: (Moderate) Corticosteroids may accentuate the electrolyte loss associated with diuretic therapy resulting in hypokalemia and/or hypomagnesemia. While glucocorticoids with mineralocorticoid activity (e.g., cortisone, hydrocortisone) can cause sodium and fluid retention. Close monitoring of electrolytes should occur in patients receiving these drugs concomitantly.
    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) Concomitant use of a thiazide diuretiic, or the related drug metolazone, with a loop diuretic can cause additive electrolyte and fluid loss. In patients with creatinine clearances > 30 ml/min, the combinations may also lead to profound fluid and electrolyte loss in some patients. Thus, use cautiously and with monitoring of renal function, blood pressure, cardiac status, electrolytes (especially potassium), and monitor the clinical response for the condition treated.
    Bosentan: (Moderate) Although no specific interactions have been documented, bosentan has vasodilatory effects and may contribute additive hypotensive effects when given with diuretics.
    Brexpiprazole: (Moderate) Due to brexpiprazole's antagonism at alpha 1-adrenergic receptors, the drug may enhance the hypotensive effects of alpha-blockers and other antihypertensive agents.
    Bromocriptine: (Minor) Bromocriptine has only minimal affinity for adrenergic receptors; however, hypotension can occur during bromocriptine administration. Orthostatic hypotension occurs in 6% of acromegaly patients receiving the drug. Hypotension occurred frequently (approximately 30%) in postpartum studies, which in rare cases approached a decline in supine pressure of almost 60 mmHg. It is unknown if bromocriptine is the exact cause of this effect. However, the drug should be used cautiously with other medications known to lower blood pressure such as antihypertensive agents. Monitoring of blood pressure should be considered, especially during the initial weeks of concomitant therapy.
    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; Hydrocodone; 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: (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) Corticosteroids may accentuate the electrolyte loss associated with diuretic therapy resulting in hypokalemia and/or hypomagnesemia. While glucocorticoids with mineralocorticoid activity (e.g., cortisone, hydrocortisone) can cause sodium and fluid retention. Close monitoring of electrolytes should occur in patients receiving these drugs concomitantly.
    Budesonide; Formoterol: (Moderate) Corticosteroids may accentuate the electrolyte loss associated with diuretic therapy resulting in hypokalemia and/or hypomagnesemia. While glucocorticoids with mineralocorticoid activity (e.g., cortisone, hydrocortisone) can cause sodium and fluid retention. Close monitoring of electrolytes should occur in patients receiving these drugs concomitantly.
    Cabergoline: (Minor) Cabergoline has minimal affinity for adrenergic receptors; however, it has been associated with hypotension in some instances. Cabergoline should be used cautiously in those receiving antihypertensive agents.
    Calcium Carbonate; Magnesium Hydroxide: (Moderate) 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.
    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: (Moderate) When canagliflozin is initiated in patients already receiving diuretics, symptomatic hypotension can occur. Patients with impaired renal function (eGFR < 60 ml/min/1.73 m2), low systolic blood pressure, or who are elderly may also be at a greater risk. Before initiating canagliflozin in patients with one or more of these characteristics, volume status should be assessed and corrected. Monitor for signs and symptoms after initiating therapy. In addition, loop diuretics can also decrease the hypoglycemic effects of antidiabetic agents by producing an increase in blood glucose concentrations. Patients receiving canagliflozin should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary.
    Canagliflozin; Metformin: (Moderate) Loop diuretics can decrease the hypoglycemic effects of antidiabetic agents by producing an increase in blood glucose concentrations.Patients receiving antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. (Moderate) When canagliflozin is initiated in patients already receiving diuretics, symptomatic hypotension can occur. Patients with impaired renal function (eGFR < 60 ml/min/1.73 m2), low systolic blood pressure, or who are elderly may also be at a greater risk. Before initiating canagliflozin in patients with one or more of these characteristics, volume status should be assessed and corrected. Monitor for signs and symptoms after initiating therapy. In addition, loop diuretics can also decrease the hypoglycemic effects of antidiabetic agents by producing an increase in blood glucose concentrations. Patients receiving canagliflozin should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary.
    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) Concomitant use of a thiazide diuretiic, or the related drug metolazone, with a loop diuretic can cause additive electrolyte and fluid loss. In patients with creatinine clearances > 30 ml/min, the combinations may also lead to profound fluid and electrolyte loss in some patients. Thus, use cautiously and with monitoring of renal function, blood pressure, cardiac status, electrolytes (especially potassium), and monitor the clinical response for the condition treated.
    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: (Moderate) Coadministration of loop diuretics and Angiotensin-converting enzyme inhibitors (ACE inhibitors) 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.
    Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Coadministration of loop diuretics and Angiotensin-converting enzyme inhibitors (ACE inhibitors) 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) Concomitant use of a thiazide diuretiic, or the related drug metolazone, with a loop diuretic can cause additive electrolyte and fluid loss. In patients with creatinine clearances > 30 ml/min, the combinations may also lead to profound fluid and electrolyte loss in some patients. Thus, use cautiously and with monitoring of renal function, blood pressure, cardiac status, electrolytes (especially potassium), and monitor the clinical response for the condition treated.
    Carbenicillin: (Minor) Ethacrynic acid 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.
    Carbetapentane; Chlorpheniramine; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Carbetapentane; Diphenhydramine; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Carbetapentane; Guaifenesin; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Carbetapentane; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Carbetapentane; Phenylephrine; Pyrilamine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Carbetapentane; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Carbidopa; Levodopa: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
    Carbidopa; Levodopa; Entacapone: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Moderate) 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) Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs such as loop diuretics, increasing the risk of proarrhythmic effects of cardiac glycosides. Potassium levels should be monitored and normalized prior to and during concurrent diuretic administration and these agents.
    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.
    Casanthranol; Docusate Sodium: (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.
    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: (Moderate) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant furosemide therapy. Clinicans should be aware that this may occur even in patients with minor or transient renal impairment.
    Cefadroxil: (Severe) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant furosemide therapy. Clinicans should be aware that this may occur even in patients with minor or transient renal impairment.
    Cefazolin: (Moderate) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant furosemide therapy. Clinicans should be aware that this may occur even in patients with minor or transient renal impairment.
    Cefdinir: (Moderate) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant furosemide therapy. Clinicans should be aware that this may occur even in patients with minor or transient renal impairment.
    Cefditoren: (Moderate) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant furosemide therapy. Clinicans should be aware that this may occur even in patients with minor or transient renal impairment.
    Cefepime: (Minor) Cefepime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
    Cefixime: (Moderate) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant furosemide therapy. Clinicans should be aware that this may occur even in patients with minor or transient renal impairment.
    Cefoperazone: (Moderate) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant furosemide therapy. Clinicans should be aware that this may occur even in patients with minor or transient renal impairment.
    Cefotaxime: (Minor) Cefotaxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
    Cefotetan: (Moderate) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant furosemide therapy. Clinicans should be aware that this may occur even in patients with minor or transient renal impairment.
    Cefoxitin: (Moderate) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant furosemide therapy. Clinicans should be aware that this may occur even in patients with minor or transient renal impairment.
    Cefpodoxime: (Moderate) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant furosemide therapy. Clinicans should be aware that this may occur even in patients with minor or transient renal impairment.
    Cefprozil: (Minor) Cefprozil's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
    Ceftaroline: (Moderate) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant furosemide therapy. Clinicans should be aware that this may occur even in patients with minor or transient renal impairment.
    Ceftazidime: (Minor) Ceftazidime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
    Ceftazidime; Avibactam: (Minor) Ceftazidime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
    Ceftibuten: (Moderate) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant furosemide therapy. Clinicans should be aware that this may occur even in patients with minor or transient renal impairment.
    Ceftizoxime: (Moderate) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant furosemide therapy. Clinicans should be aware that this may occur even in patients with minor or transient renal impairment.
    Ceftriaxone: (Moderate) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant furosemide therapy. Clinicans should be aware that this may occur even in patients with minor or transient renal impairment.
    Cefuroxime: (Minor) Cefuroxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
    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.
    Cephalexin: (Moderate) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant furosemide therapy. Clinicans should be aware that this may occur even in patients with minor or transient renal impairment.
    Cephradine: (Moderate) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant furosemide therapy. Clinicans 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) Concomitant use of a thiazide diuretiic, or the related drug metolazone, with a loop diuretic can cause additive electrolyte and fluid loss. In patients with creatinine clearances > 30 ml/min, the combinations may also lead to profound fluid and electrolyte loss in some patients. Thus, use cautiously and with monitoring of renal function, blood pressure, cardiac status, electrolytes (especially potassium), and monitor the clinical response for the condition treated.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Chlorpheniramine; Hydrocodone; 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; 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; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Chlorpheniramine; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Chlorthalidone: (Moderate) Concomitant use of a thiazide diuretiic, or the related drug metolazone, with a loop diuretic can cause additive electrolyte and fluid loss. In patients with creatinine clearances > 30 ml/min, the combinations may also lead to profound fluid and electrolyte loss in some patients. Thus, use cautiously and with monitoring of renal function, blood pressure, cardiac status, electrolytes (especially potassium), and monitor the clinical response for the condition treated.
    Chlorthalidone; Clonidine: (Moderate) Concomitant use of a thiazide diuretiic, or the related drug metolazone, with a loop diuretic can cause additive electrolyte and fluid loss. In patients with creatinine clearances > 30 ml/min, the combinations may also lead to profound fluid and electrolyte loss in some patients. Thus, use cautiously and with monitoring of renal function, blood pressure, cardiac status, electrolytes (especially potassium), and monitor the clinical response for the condition treated.
    Ciclesonide: (Moderate) Corticosteroids may accentuate the electrolyte loss associated with diuretic therapy resulting in hypokalemia and/or hypomagnesemia. While glucocorticoids with mineralocorticoid activity (e.g., cortisone, hydrocortisone) can cause sodium and fluid retention. Close monitoring of electrolytes should occur in patients receiving these drugs concomitantly.
    Cidofovir: (Severe) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir.
    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) Furosemide-induced hypokalemia can potentiate neuromuscular blockade with nondepolarizing neuromuscular blockers. In addition, furosemide may antagonize the skeletal muscle relaxing effect of tubocurarine and can potentiate neuromuscular blockade following succinylcholine administration.
    Cisplatin: (Moderate) Concurrent use of cisplatin and other agents known to be ototoxic (e.g., loop diuretics) may increase the risk of drug-induced ototoxicity, but confirmatory data are not available. Usually, reports indicate that furosemide ototoxicity is associated with rapid injection, severe renal impairment, higher than recommended furosemide dosages or infusion rates, hypoproteinemia, or concomitant therapy with other ototoxic drugs. Additive effects of cisplatin and loop diuretics on renal parameters and electrolyte balance should also be considered. Saline hydration and diuretic use are common during cisplatin therapy to manage hydration status. If furosemide and cisplatin are used together, it is prudent to monitor renal function parameters and serum electrolyte concentrations during co-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.
    Citalopram: (Moderate) Citalopram causes dose-dependent QT interval prolongation. Concurrent use of citalopram and medications known to cause electrolyte imbalance may increase the risk of developing QT prolongation. Therefore, caution is advisable during concurrent use of citalopram and diuretics. In addition, patients receiving a diuretic during treatment with citalopram may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of citalopram should be considered in patients who develop symptomatic hyponatremia.
    Clozapine: (Major) Caution is advisable during concurrent use of clozapine and loop diuretics. Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. Concurrent use of clozapine and medications known to cause electrolyte imbalance may increase the risk of QT prolongation.
    Cod Liver Oil: (Moderate) Fish oil supplements may cause mild, dose-dependent reductions in systolic or diastolic blood pressure in untreated hypertensive patients. Relatively high doses of fish oil are required to produce any blood pressure lowering effect. Additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents. (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
    Codeine; Phenylephrine; Promethazine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Co-Enzyme Q10, Ubiquinone: (Moderate) Co-enzyme Q10, ubiquinone (CoQ10) may lower blood pressure. CoQ10 use in combination with antihypertensive agents may lead to additional reductions in blood pressure in some individuals. Patients who choose to take CoQ10 concurrently with antihypertensive medications should receive periodic blood pressure monitoring. Patients should be advised to inform their prescriber of their use of CoQ10.
    Conivaptan: (Moderate) There is potential for additive hypotensive effects when conivaptan is coadministered with antihypertensive agents.
    Corticosteroids: (Moderate) Corticosteroids may accentuate the electrolyte loss associated with diuretic therapy resulting in hypokalemia and/or hypomagnesemia. While glucocorticoids with mineralocorticoid activity (e.g., cortisone, hydrocortisone) can cause sodium and fluid retention. Close monitoring of electrolytes should occur in patients receiving these drugs concomitantly.
    Corticotropin, ACTH: (Moderate) Corticosteroids may accentuate the electrolyte loss associated with diuretic therapy resulting in hypokalemia and/or hypomagnesemia. While glucocorticoids with mineralocorticoid activity (e.g., cortisone, hydrocortisone) can cause sodium and fluid retention. Close monitoring of electrolytes should occur in patients receiving these drugs concomitantly.
    Cortisone: (Moderate) Corticosteroids may accentuate the electrolyte loss associated with diuretic therapy resulting in hypokalemia and/or hypomagnesemia. While glucocorticoids with mineralocorticoid activity (e.g., cortisone, hydrocortisone) can cause sodium and fluid retention. Close monitoring of electrolytes should occur in patients receiving these drugs concomitantly.
    Cosyntropin: (Moderate) Use cosyntropin cautiously in patients receiving diuretics. Cosyntropin may accentuate the electrolyte loss associated with diuretic therapy.
    Dapagliflozin: (Moderate) Loop diuretics can decrease the hypoglycemic effects of antidiabetic agents by producing an increase in blood glucose concentrations. Patients receiving dapagliflozin should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary.
    Dapagliflozin; Metformin: (Moderate) Loop diuretics can decrease the hypoglycemic effects of antidiabetic agents by producing an increase in blood glucose concentrations. Patients receiving dapagliflozin should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. (Moderate) Loop diuretics can decrease the hypoglycemic effects of antidiabetic agents by producing an increase in blood glucose concentrations.Patients receiving antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary.
    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.
    Darifenacin: (Minor) Diuretics can increase urinary frequency, which may aggravate bladder symptoms.
    Deflazacort: (Moderate) Corticosteroids may accentuate the electrolyte loss associated with diuretic therapy resulting in hypokalemia and/or hypomagnesemia. While glucocorticoids with mineralocorticoid activity (e.g., cortisone, hydrocortisone) can cause sodium and fluid retention. Close monitoring of electrolytes should occur in patients receiving these drugs concomitantly.
    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: (Major) Desmopressin, when used in the treatment of nocturia is contraindicated with loop diuretics because of the risk of severe hyponatremia.
    Desvenlafaxine: (Moderate) Patients receiving a diuretic during treatment with venlafaxine may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH may occur during therapy with SNRIs, including venlafaxine. Cases involving serum sodium levels lower than 110 mmol/l have been reported. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of the SNRI should be considered in patients who develop symptomatic hyponatremia.
    Dexamethasone: (Moderate) Corticosteroids may accentuate the electrolyte loss associated with diuretic therapy resulting in hypokalemia and/or hypomagnesemia. While glucocorticoids with mineralocorticoid activity (e.g., cortisone, hydrocortisone) can cause sodium and fluid retention. Close monitoring of electrolytes should occur in patients receiving these drugs concomitantly.
    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.
    Dexmethylphenidate: (Moderate) Dexmethylphenidate can reduce the hypotensive effect of antihypertensive agents, including loop diuretics. Periodic evaluation of blood pressure is advisable during concurrent use of dexmethylphenidate and antihypertensive agents, particularly during initial coadministration and after dosage increases of dexmethylphenidate.
    Dextroamphetamine: (Major) 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 or the selection of alternative therapeutic agents may be needed.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Dextromethorphan; Quinidine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Diazoxide: (Moderate) Additive hypotensive effects can occur with the concomitant administration of diazoxide with loop diuretics. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly. The manufacturer advises that IV diazoxide should not be administered to patients within 6 hours of receiving other antihypertensive agents.
    Dichlorphenamide: (Moderate) Use dichlorphenamide and diuretics together with caution. Dichlorphenamide increases potassium excretion and can cause hypokalemia and should be used cautiously with other drugs that may cause hypokalemia including loop diuretics and thiazide diuretics. Measure potassium concentrations at baseline and periodically during dichlorphenamide treatment. If hypokalemia occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy.
    Diclofenac: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain.
    Diclofenac; Misoprostol: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain.
    Dicloxacillin: (Minor) Ethacrynic acid 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) Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs such as loop diuretics, increasing the risk of proarrhythmic effects of cardiac glycosides. Potassium levels should be monitored and normalized prior to and during concurrent diuretic administration and these agents.
    Digoxin: (Moderate) Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs such as loop diuretics, increasing the risk of proarrhythmic effects of cardiac glycosides. Potassium levels should be monitored and normalized prior to and during concurrent diuretic administration and these agents.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Diphenhydramine; Ibuprofen: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain.
    Diphenhydramine; Naproxen: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain.
    Diphenhydramine; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Docusate Sodium; Senna: (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.
    Docusate: (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.
    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: (Major) The manufacturer warns that the coadministration of dolasetron with diuretics associated with hypokalemia could increase the risk of QT prolongation. 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 increasing the potential for cardiac arrhythmias. Potassium levels should be within the normal range prior to and during therapy with dolasetron.
    Doxacurium: (Moderate) Furosemide-induced hypokalemia can potentiate neuromuscular blockade with nondepolarizing neuromuscular blockers. In addition, furosemide may antagonize the skeletal muscle relaxing effect of tubocurarine and can potentiate neuromuscular blockade following succinylcholine administration.
    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) Patients receiving a diuretic during treatment with venlafaxine may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH may occur during therapy with SNRIs, including venlafaxine. Cases involving serum sodium levels lower than 110 mmol/l have been reported. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of the SNRI should be considered in patients who develop symptomatic 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; Metformin: (Moderate) Loop diuretics can decrease the hypoglycemic effects of antidiabetic agents by producing an increase in blood glucose concentrations.Patients receiving antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. (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.
    Enalapril, Enalaprilat: (Moderate) Coadministration of loop diuretics and Angiotensin-converting enzyme inhibitors (ACE inhibitors) 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.
    Enalapril; Felodipine: (Moderate) Coadministration of loop diuretics and Angiotensin-converting enzyme inhibitors (ACE inhibitors) 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.
    Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Coadministration of loop diuretics and Angiotensin-converting enzyme inhibitors (ACE inhibitors) 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) Concomitant use of a thiazide diuretiic, or the related drug metolazone, with a loop diuretic can cause additive electrolyte and fluid loss. In patients with creatinine clearances > 30 ml/min, the combinations may also lead to profound fluid and electrolyte loss in some patients. Thus, use cautiously and with monitoring of renal function, blood pressure, cardiac status, electrolytes (especially potassium), and monitor the clinical response for the condition treated.
    Enflurane: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    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.
    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) Concomitant use of a thiazide diuretiic, or the related drug metolazone, with a loop diuretic can cause additive electrolyte and fluid loss. In patients with creatinine clearances > 30 ml/min, the combinations may also lead to profound fluid and electrolyte loss in some patients. Thus, use cautiously and with monitoring of renal function, blood pressure, cardiac status, electrolytes (especially potassium), and monitor the clinical response for the condition treated.
    Escitalopram: (Moderate) Patients receiving a diuretic during treatment with escitalopram may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of escitalopram should be considered in patients who develop symptomatic hyponatremia.
    Esomeprazole: (Moderate) Proton pump inhibitors, such as esomeprazole, 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.
    Esomeprazole; Naproxen: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. (Moderate) Proton pump inhibitors, such as esomeprazole, 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.
    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.
    Ethanol: (Moderate) Ethanol, since it also possesses diuretic properties, should be taken in small quantities in patients receiving loop diuretics. The diuretic properties may be additive, leading to dehydration in some patients. In addition, ethanol has hypotensive properties which can enhance the antihypertensive effects of diuretics.
    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.
    Famotidine; Ibuprofen: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain.
    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) Fentanyl may reduce the efficacy of diuretics due to induction of the release of antidiuretic hormone. Adjustments to diuretic therapy may be needed in some patients. In addition, opiate agonists may potentiate orthostatic hypotension when used concurrently with diuretics.
    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) Co-enzyme Q10, ubiquinone (CoQ10) may lower blood pressure. CoQ10 use in combination with antihypertensive agents may lead to additional reductions in blood pressure in some individuals. Patients who choose to take CoQ10 concurrently with antihypertensive medications should receive periodic blood pressure monitoring. Patients should be advised to inform their prescriber of their use of CoQ10. (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
    Fludrocortisone: (Moderate) Corticosteroids may accentuate the electrolyte loss associated with diuretic therapy resulting in hypokalemia and/or hypomagnesemia. While glucocorticoids with mineralocorticoid activity (e.g., cortisone, hydrocortisone) can cause sodium and fluid retention. Close monitoring of electrolytes should occur in patients receiving these drugs concomitantly.
    Flunisolide: (Moderate) Corticosteroids may accentuate the electrolyte loss associated with diuretic therapy resulting in hypokalemia and/or hypomagnesemia. While glucocorticoids with mineralocorticoid activity (e.g., cortisone, hydrocortisone) can cause sodium and fluid retention. Close monitoring of electrolytes should occur in patients receiving these drugs concomitantly.
    Fluoxetine: (Moderate) Patients receiving a diuretic during treatment with fluoxetine may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of fluoxetine should be considered in patients who develop symptomatic hyponatremia.
    Fluoxetine; Olanzapine: (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents. (Moderate) Patients receiving a diuretic during treatment with fluoxetine may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of fluoxetine should be considered in patients who develop symptomatic hyponatremia.
    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) Corticosteroids may accentuate the electrolyte loss associated with diuretic therapy resulting in hypokalemia and/or hypomagnesemia. While glucocorticoids with mineralocorticoid activity (e.g., cortisone, hydrocortisone) can cause sodium and fluid retention. Close monitoring of electrolytes should occur in patients receiving these drugs concomitantly.
    Fluticasone; Salmeterol: (Moderate) Corticosteroids may accentuate the electrolyte loss associated with diuretic therapy resulting in hypokalemia and/or hypomagnesemia. While glucocorticoids with mineralocorticoid activity (e.g., cortisone, hydrocortisone) can cause sodium and fluid retention. Close monitoring of electrolytes should occur in patients receiving these drugs concomitantly.
    Fluticasone; Umeclidinium; Vilanterol: (Moderate) Corticosteroids may accentuate the electrolyte loss associated with diuretic therapy resulting in hypokalemia and/or hypomagnesemia. While glucocorticoids with mineralocorticoid activity (e.g., cortisone, hydrocortisone) can cause sodium and fluid retention. Close monitoring of electrolytes should occur in patients receiving these drugs concomitantly.
    Fluticasone; Vilanterol: (Moderate) Corticosteroids may accentuate the electrolyte loss associated with diuretic therapy resulting in hypokalemia and/or hypomagnesemia. While glucocorticoids with mineralocorticoid activity (e.g., cortisone, hydrocortisone) can cause sodium and fluid retention. Close monitoring of electrolytes should occur in patients receiving these drugs concomitantly.
    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) Corticosteroids may accentuate the electrolyte loss associated with diuretic therapy resulting in hypokalemia and/or hypomagnesemia. While glucocorticoids with mineralocorticoid activity (e.g., cortisone, hydrocortisone) can cause sodium and fluid retention. Close monitoring of electrolytes should occur in patients receiving these drugs concomitantly.
    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: (Moderate) Coadministration of loop diuretics and Angiotensin-converting enzyme inhibitors (ACE inhibitors) 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.
    Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Coadministration of loop diuretics and Angiotensin-converting enzyme inhibitors (ACE inhibitors) 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) Concomitant use of a thiazide diuretiic, or the related drug metolazone, with a loop diuretic can cause additive electrolyte and fluid loss. In patients with creatinine clearances > 30 ml/min, the combinations may also lead to profound fluid and electrolyte loss in some patients. Thus, use cautiously and with monitoring of renal function, blood pressure, cardiac status, electrolytes (especially potassium), and monitor the clinical response for the condition treated.
    Fospropofol: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Gallium Ga 68 Dotatate: (Moderate) Mannitol can potentiate the effects of other diuretics when these drugs are administered concurrently.
    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; Pioglitazone: (Moderate) Loop diuretics can decrease the hypoglycemic effects of antidiabetic agents by producing an increase in blood glucose concentrations. Patients receiving antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary.
    Glipizide; Metformin: (Moderate) Loop diuretics can decrease the hypoglycemic effects of antidiabetic agents by producing an increase in blood glucose concentrations.Patients receiving antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary.
    Glyburide; Metformin: (Moderate) Loop diuretics can decrease the hypoglycemic effects of antidiabetic agents by producing an increase in blood glucose concentrations.Patients receiving antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary.
    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; 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.
    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.
    Halofantrine: (Major) Due to the risks of cardiac toxicity of halofantrine in patients with hypokalemia and/or hypomagnesemia, the use of halofantrine should be avoided when feasible in those patients receiving potassium-wasting diuretic therapies such as loop diuretics.
    Haloperidol: (Major) QT prolongation has been observed during haloperidol treatment. Use of haloperidol and medications known to cause electrolyte imbalance may increase the risk of QT prolongation. Therefore, caution is advisable during concurrent use of haloperidol and loop diuretics. In general, haloperidol should also be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
    Halothane: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Hawthorn, Crataegus laevigata: (Moderate) Hawthorn, Crataegus laevigata may lower peripheral vascular resistance. Hawthorn use in combination with antihypertensive agents may lead to additional reductions in blood pressure in some individuals. Patients receiving hawthorn concurrently with antihypertensive medications should receive periodic blood pressure monitoring.
    Hydralazine; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of a thiazide diuretiic, or the related drug metolazone, with a loop diuretic can cause additive electrolyte and fluid loss. In patients with creatinine clearances > 30 ml/min, the combinations may also lead to profound fluid and electrolyte loss in some patients. Thus, use cautiously and with monitoring of renal function, blood pressure, cardiac status, electrolytes (especially potassium), and monitor the clinical response for the condition treated.
    Hydralazine; Isosorbide Dinitrate, ISDN: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
    Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of a thiazide diuretiic, or the related drug metolazone, with a loop diuretic can cause additive electrolyte and fluid loss. In patients with creatinine clearances > 30 ml/min, the combinations may also lead to profound fluid and electrolyte loss in some patients. Thus, use cautiously and with monitoring of renal function, blood pressure, cardiac status, electrolytes (especially potassium), and monitor the clinical response for the condition treated.
    Hydrochlorothiazide, HCTZ; 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. (Moderate) Concomitant use of a thiazide diuretiic, or the related drug metolazone, with a loop diuretic can cause additive electrolyte and fluid loss. In patients with creatinine clearances > 30 ml/min, the combinations may also lead to profound fluid and electrolyte loss in some patients. Thus, use cautiously and with monitoring of renal function, blood pressure, cardiac status, electrolytes (especially potassium), and monitor the clinical response for the condition treated.
    Hydrochlorothiazide, HCTZ; Lisinopril: (Moderate) Coadministration of loop diuretics and Angiotensin-converting enzyme inhibitors (ACE inhibitors) 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) Concomitant use of a thiazide diuretiic, or the related drug metolazone, with a loop diuretic can cause additive electrolyte and fluid loss. In patients with creatinine clearances > 30 ml/min, the combinations may also lead to profound fluid and electrolyte loss in some patients. Thus, use cautiously and with monitoring of renal function, blood pressure, cardiac status, electrolytes (especially potassium), and monitor the clinical response for the condition treated.
    Hydrochlorothiazide, HCTZ; 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. (Moderate) Concomitant use of a thiazide diuretiic, or the related drug metolazone, with a loop diuretic can cause additive electrolyte and fluid loss. In patients with creatinine clearances > 30 ml/min, the combinations may also lead to profound fluid and electrolyte loss in some patients. Thus, use cautiously and with monitoring of renal function, blood pressure, cardiac status, electrolytes (especially potassium), and monitor the clinical response for the condition treated.
    Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) Concomitant use of a thiazide diuretiic, or the related drug metolazone, with a loop diuretic can cause additive electrolyte and fluid loss. In patients with creatinine clearances > 30 ml/min, the combinations may also lead to profound fluid and electrolyte loss in some patients. Thus, use cautiously and with monitoring of renal function, blood pressure, cardiac status, electrolytes (especially potassium), and monitor the clinical response for the condition treated.
    Hydrochlorothiazide, HCTZ; Metoprolol: (Moderate) Concomitant use of a thiazide diuretiic, or the related drug metolazone, with a loop diuretic can cause additive electrolyte and fluid loss. In patients with creatinine clearances > 30 ml/min, the combinations may also lead to profound fluid and electrolyte loss in some patients. Thus, use cautiously and with monitoring of renal function, blood pressure, cardiac status, electrolytes (especially potassium), and monitor the clinical response for the condition treated.
    Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Coadministration of loop diuretics and Angiotensin-converting enzyme inhibitors (ACE inhibitors) 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) Concomitant use of a thiazide diuretiic, or the related drug metolazone, with a loop diuretic can cause additive electrolyte and fluid loss. In patients with creatinine clearances > 30 ml/min, the combinations may also lead to profound fluid and electrolyte loss in some patients. Thus, use cautiously and with monitoring of renal function, blood pressure, cardiac status, electrolytes (especially potassium), and monitor the clinical response for the condition treated.
    Hydrochlorothiazide, HCTZ; 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. (Moderate) Concomitant use of a thiazide diuretiic, or the related drug metolazone, with a loop diuretic can cause additive electrolyte and fluid loss. In patients with creatinine clearances > 30 ml/min, the combinations may also lead to profound fluid and electrolyte loss in some patients. Thus, use cautiously and with monitoring of renal function, blood pressure, cardiac status, electrolytes (especially potassium), and monitor the clinical response for the condition treated.
    Hydrochlorothiazide, HCTZ; Propranolol: (Moderate) Concomitant use of a thiazide diuretiic, or the related drug metolazone, with a loop diuretic can cause additive electrolyte and fluid loss. In patients with creatinine clearances > 30 ml/min, the combinations may also lead to profound fluid and electrolyte loss in some patients. Thus, use cautiously and with monitoring of renal function, blood pressure, cardiac status, electrolytes (especially potassium), and monitor the clinical response for the condition treated.
    Hydrochlorothiazide, HCTZ; Quinapril: (Moderate) Coadministration of loop diuretics and Angiotensin-converting enzyme inhibitors (ACE inhibitors) 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) Concomitant use of a thiazide diuretiic, or the related drug metolazone, with a loop diuretic can cause additive electrolyte and fluid loss. In patients with creatinine clearances > 30 ml/min, the combinations may also lead to profound fluid and electrolyte loss in some patients. Thus, use cautiously and with monitoring of renal function, blood pressure, cardiac status, electrolytes (especially potassium), and monitor the clinical response for the condition treated.
    Hydrochlorothiazide, HCTZ; Spironolactone: (Moderate) Concomitant use of a thiazide diuretiic, or the related drug metolazone, with a loop diuretic can cause additive electrolyte and fluid loss. In patients with creatinine clearances > 30 ml/min, the combinations may also lead to profound fluid and electrolyte loss in some patients. Thus, use cautiously and with monitoring of renal function, blood pressure, cardiac status, electrolytes (especially potassium), and monitor the clinical response for the condition treated.
    Hydrochlorothiazide, HCTZ; 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. (Moderate) Concomitant use of a thiazide diuretiic, or the related drug metolazone, with a loop diuretic can cause additive electrolyte and fluid loss. In patients with creatinine clearances > 30 ml/min, the combinations may also lead to profound fluid and electrolyte loss in some patients. Thus, use cautiously and with monitoring of renal function, blood pressure, cardiac status, electrolytes (especially potassium), and monitor the clinical response for the condition treated.
    Hydrochlorothiazide, HCTZ; Triamterene: (Moderate) Concomitant use of a thiazide diuretiic, or the related drug metolazone, with a loop diuretic can cause additive electrolyte and fluid loss. In patients with creatinine clearances > 30 ml/min, the combinations may also lead to profound fluid and electrolyte loss in some patients. Thus, use cautiously and with monitoring of renal function, blood pressure, cardiac status, electrolytes (especially potassium), and monitor the clinical response for the condition treated.
    Hydrochlorothiazide, HCTZ; 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. (Moderate) Concomitant use of a thiazide diuretiic, or the related drug metolazone, with a loop diuretic can cause additive electrolyte and fluid loss. In patients with creatinine clearances > 30 ml/min, the combinations may also lead to profound fluid and electrolyte loss in some patients. Thus, use cautiously and with monitoring of renal function, blood pressure, cardiac status, electrolytes (especially potassium), and monitor the clinical response for the condition treated.
    Hydrocodone; Ibuprofen: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain.
    Hydrocodone; 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.
    Hydrocodone; Potassium Guaiacolsulfonate; 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.
    Hydrocodone; 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.
    Hydrocortisone: (Moderate) Corticosteroids may accentuate the electrolyte loss associated with diuretic therapy resulting in hypokalemia and/or hypomagnesemia. While glucocorticoids with mineralocorticoid activity (e.g., cortisone, hydrocortisone) can cause sodium and fluid retention. Close monitoring of electrolytes should occur in patients receiving these drugs concomitantly.
    Ibandronate: (Moderate) When the intravenous formulation of ibandronate is used for the treatment of hypercalcemia of malignancy, combination therapy with loop diuretics should be used with caution in order to avoid hypocalcemia. In patients with hypercalcemia of malignancy, the initial treatment typically includes the use of loop diuretics, in combination with saline hydration, however, diuretic therapy should not be employed prior to correction of hypovolemia and dehydration.
    Ibuprofen lysine: (Moderate) Ibuprofen lysine may reduce the effect of diuretics; diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated patients. During coadministration of NSAIDs and diuretic therapy, patients should be monitored for changes in the effectiveness of their diuretic therapy and for signs and symptoms of renal impairment.
    Ibuprofen: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain.
    Ibuprofen; Oxycodone: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain.
    Ibuprofen; Pseudoephedrine: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Ifosfamide: (Moderate) Nephrotoxic agents, such as the loop diuretics, can increase the nephrotoxicity of ifosfamide. Clinicians should be alert for an increased risk of ifosfamide toxicity, including neurotoxicity, kidney toxicity, and bone marrow suppression.
    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.
    Inamrinone: (Moderate) Hypokalemia may occur due to excessive diuresis during inamrinone therapy. Fluid and electrolyte changes and renal function should be carefully monitored during inamrinone therapy.
    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.
    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.
    Intravenous Lipid Emulsions: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
    Irbesartan: (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.
    Irinotecan: (Moderate) Volume depletion due to irinotecan-induced vomiting or diarrhea can be exacerbated by diuretics. Withholding diuretics during irinotecan dosing, especially during periods of active vomiting or diarrhea, may be desirable.
    Isocarboxazid: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Isoflurane: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Isoproterenol: (Moderate) The pharmacologic effects of isoproterenol may cause an increase in blood pressure. If isoproterenol is used concomitantly with antihypertensives, the blood pressure should be monitored as the administration of isoproterenol can compromise the effectiveness of antihypertensive agents.
    Isosorbide Dinitrate, ISDN: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
    Isosorbide Mononitrate: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
    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) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain.
    Lactulose: (Moderate) Loop diuretics may increase the risk of hypokalemia especially in patients receiving prolonged therapy with laxatives. Monitor serum potassium levels to determine the need for potassium supplementation and/or alteration in drug therapy.
    Lansoprazole: (Moderate) 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.
    Lansoprazole; Naproxen: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. (Moderate) 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.
    Levodopa: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
    Levomethadyl: (Moderate) Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs such as loop diuretics, increasing the risk of proarrhythmic effects of levomethadyl. Potassium levels should be monitored and normalized prior to and during concurrent diuretic administration and these agents.
    Levomilnacipran: (Moderate) Patients receiving a diuretic during treatment with venlafaxine may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH may occur during therapy with SNRIs, including venlafaxine. Cases involving serum sodium levels lower than 110 mmol/l have been reported. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of the SNRI should be considered in patients who develop symptomatic hyponatremia.
    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: (Moderate) Loop diuretics can decrease the hypoglycemic effects of antidiabetic agents by producing an increase in blood glucose concentrations.Patients receiving antidiabetic agents 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.
    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: (Major) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Lisinopril: (Moderate) Coadministration of loop diuretics and Angiotensin-converting enzyme inhibitors (ACE inhibitors) 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.
    Lithium: (Moderate) Loop diuretics may increase serum lithium concentrations by increasing lithium reabsorption in the proximal tubule, and possibly by decreasing lithium reabsorption in the loop of Henle with an increase in lithium delivery to the distal tubule with minor compensatory reabsorption. However, the effect of loop diuretics on lithium clearance relative to thiazide diuretics is generally minor. In one small study evaluating the pharmacokinetic effects of several different medications on a single 600 mg dose of lithium carbonate, administration of furosemide resulted in an 11% decrease in lithium clearance. According to the Beers Criteria, concurrent use of lithium and loop diuretics may result in a clinically important drug interaction, particularly in older adults. The Beers expert panel recommends avoiding concurrent use due to an increased risk of lithium toxicity. If the combination is necessary, monitoring of lithium concentrations is recommended.
    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.
    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) 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.
    Magnesium Hydroxide: (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.
    Magnesium Salts: (Moderate) Diuretics may interfere with the kidneys ability to regulate magnesium concentrations. Long-term use of diuretics may impair the magnesium-conserving ability of the kidneys and lead to hypomagnesemia. (Moderate) Diuretics may interfere with the kidneys ability to regulate magnesium concentrations. Long-term use of loop diuretics may impair the magnesium-conserving ability of the kidneys and lead to hypomagnesemia. In addition, use caution when prescribing sulfate salt bowel preparation in patients taking concomitant medications that may affect renal function such as diuretics.
    Magnesium Sulfate; Potassium Sulfate; Sodium Sulfate: (Moderate) Use caution when prescribing sulfate salt bowel preparation in patients taking concomitant medications that may affect renal function such as diuretics.
    Mannitol: (Moderate) Mannitol can potentiate the effects of other diuretics when these drugs are administered concurrently.
    Meclofenamate Sodium: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain.
    Mefenamic Acid: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain.
    Meglitinides: (Minor) Loop diuretics have been associated with hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between loop diuretics and all antidiabetic agents. Monitor for a loss of diabetic control.
    Meloxicam: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain.
    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: (Moderate) Loop diuretics can decrease the hypoglycemic effects of antidiabetic agents by producing an increase in blood glucose concentrations.Patients receiving antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary.
    Metformin; Pioglitazone: (Moderate) Loop diuretics can decrease the hypoglycemic effects of antidiabetic agents by producing an increase in blood glucose concentrations. Patients receiving antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. (Moderate) Loop diuretics can decrease the hypoglycemic effects of antidiabetic agents by producing an increase in blood glucose concentrations.Patients receiving antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary.
    Metformin; Repaglinide: (Moderate) Loop diuretics can decrease the hypoglycemic effects of antidiabetic agents by producing an increase in blood glucose concentrations.Patients receiving antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. (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: (Moderate) Loop diuretics can decrease the hypoglycemic effects of antidiabetic agents by producing an increase in blood glucose concentrations.Patients receiving antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary.
    Metformin; Saxagliptin: (Moderate) Loop diuretics can decrease the hypoglycemic effects of antidiabetic agents by producing an increase in blood glucose concentrations.Patients receiving antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary.
    Metformin; Sitagliptin: (Moderate) Loop diuretics can decrease the hypoglycemic effects of antidiabetic agents by producing an increase in blood glucose concentrations.Patients receiving antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary.
    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: (Major) 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 or the selection of alternative therapeutic agents may be needed.
    Methazolamide: (Moderate) Loop diuretics may increase the risk of hypokalemia if used concurrently with methazolamide. Monitor serum potassium levels to determine the need for potassium supplementation and/or alteration in drug therapy. There may also be an additive diuretic or hyperuricemic effect.
    Methohexital: (Moderate) Concurrent use of methohexital and antihypertensive agents increases the risk of developing hypotension.
    Methyclothiazide: (Moderate) Concomitant use of a thiazide diuretiic, or the related drug metolazone, with a loop diuretic can cause additive electrolyte and fluid loss. In patients with creatinine clearances > 30 ml/min, the combinations may also lead to profound fluid and electrolyte loss in some patients. Thus, use cautiously and with monitoring of renal function, blood pressure, cardiac status, electrolytes (especially potassium), and monitor the clinical response for the condition treated.
    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: (Moderate) Methylphenidate can reduce the hypotensive effect of antihypertensive agents such as loop diuretics. Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate.
    Methylprednisolone: (Moderate) Corticosteroids may accentuate the electrolyte loss associated with diuretic therapy resulting in hypokalemia and/or hypomagnesemia. While glucocorticoids with mineralocorticoid activity (e.g., cortisone, hydrocortisone) can cause sodium and fluid retention. Close monitoring of electrolytes should occur in patients receiving these drugs concomitantly.
    Metolazone: (Moderate) Concomitant use of a thiazide diuretiic, or the related drug metolazone, with a loop diuretic can cause additive electrolyte and fluid loss. In patients with creatinine clearances > 30 ml/min, the combinations may also lead to profound fluid and electrolyte loss in some patients. Thus, use cautiously and with monitoring of renal function, blood pressure, cardiac status, electrolytes (especially potassium), and monitor the clinical response for the condition treated.
    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) Patients receiving a diuretic during treatment with venlafaxine may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH may occur during therapy with SNRIs, including venlafaxine. Cases involving serum sodium levels lower than 110 mmol/l have been reported. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of the SNRI should be considered in patients who develop symptomatic hyponatremia.
    Milrinone: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
    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) Hyponatremia has been reported very rarely during mirtazapine administration. Caution is advisable in patients receiving medications known to cause hyponatremia, such as diuretics. Hyponatremia may manifest as headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness which may result in falls. Severe manifestations include hallucinations, syncope, seizure, coma, respiratory arrest, and death. Symptomatic hyponatremia may require discontinuation of mirtazapine, as well as implementation of the appropriate medical interventions.
    Mivacurium: (Moderate) Furosemide-induced hypokalemia can potentiate neuromuscular blockade with nondepolarizing neuromuscular blockers. In addition, furosemide may antagonize the skeletal muscle relaxing effect of tubocurarine and can potentiate neuromuscular blockade following succinylcholine administration.
    Moexipril: (Moderate) Coadministration of loop diuretics and Angiotensin-converting enzyme inhibitors (ACE inhibitors) 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.
    Mometasone: (Moderate) Corticosteroids may accentuate the electrolyte loss associated with diuretic therapy resulting in hypokalemia and/or hypomagnesemia. While glucocorticoids with mineralocorticoid activity (e.g., cortisone, hydrocortisone) can cause sodium and fluid retention. Close monitoring of electrolytes should occur in patients receiving these drugs concomitantly.
    Morphine: (Moderate) Morphine may reduce the efficacy of diuretics due to induction of the release of antidiuretic hormone. Morphine may also cause acute urinary retention by causing a spasm of the bladder sphincter; men with enlarged prostates may have a higher risk of this reaction.
    Morphine; Naltrexone: (Moderate) Morphine may reduce the efficacy of diuretics due to induction of the release of antidiuretic hormone. Morphine may also cause acute urinary retention by causing a spasm of the bladder sphincter; men with enlarged prostates may have a higher risk of this reaction.
    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) Ethacrynic acid 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) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain.
    Naproxen; Pseudoephedrine: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    Naproxen; Sumatriptan: (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.
    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.
    Nesiritide, BNP: (Major) The potential for hypotension may be increased when coadministering nesiritide with antihypertensive agents.
    Neuromuscular blockers: (Moderate) Furosemide-induced hypokalemia can potentiate neuromuscular blockade with nondepolarizing neuromuscular blockers. In addition, furosemide may antagonize the skeletal muscle relaxing effect of tubocurarine and can potentiate neuromuscular blockade following succinylcholine administration.
    Niacin, Niacinamide: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
    Niacin; Simvastatin: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
    Nitrates: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
    Nitroglycerin: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
    Nitroprusside: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
    Non-Ionic Contrast Media: (Moderate) Because patients should be well-hydrated prior to the administration of contrast media, loop diuretics such as furosemide that cause intravascular volume depletion might increase the risk of nephrotoxicity when using radiopaque contrast agents. In addition, furosemide plus normal saline have been evaluated for the prevention of contrast induced nephropathy; in one retrospective review, the incidence of contrast-induced nephropathy in the furosemide plus saline group was almost four times that of the saline only group (40% versus 11%, respectively). Other studies have shown no benefit with combination therapy.
    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.
    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.
    Omeprazole: (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.
    Omeprazole; Sodium Bicarbonate: (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.
    Ondansetron: (Moderate) The coadministration of ondansetron with diuretics associated with hypokalemia could increase the risk of QT prolongation. Potassium levels should be within the normal range prior to and during therapy with ondansetron.
    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) Ethacrynic acid 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.
    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.
    Paliperidone: (Moderate) Paliperidone may cause orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses of paliperidone may be necessary in patients receiving antihypertensive agents concomitantly.
    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) Furosemide-induced hypokalemia can potentiate neuromuscular blockade with nondepolarizing neuromuscular blockers. In addition, furosemide may antagonize the skeletal muscle relaxing effect of tubocurarine and can potentiate neuromuscular blockade following succinylcholine administration.
    Pantoprazole: (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.
    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) Patients receiving a diuretic during treatment with paroxetine may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of paroxetine should be considered in patients who develop symptomatic hyponatremia.
    Pasireotide: (Major) Cautious use of pasireotide and medicines that can affect potassium or magnesium concentrations such as diuretics is advised. Pasireotide may prolong the QT interval, and hypokalemia and/or hypomagnesemia are risk factors for QT prolongation. 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) Ethacrynic acid 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) Ethacrynic acid 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) Ethacrynic acid 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) Ethacrynic acid 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) Ethacrynic acid 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) Ethacrynic acid 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: (Major) 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. .
    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: (Moderate) Coadministration of loop diuretics and Angiotensin-converting enzyme inhibitors (ACE inhibitors) 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.
    Perindopril; Amlodipine: (Moderate) Coadministration of loop diuretics and Angiotensin-converting enzyme inhibitors (ACE inhibitors) 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.
    Phenelzine: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Phentermine; Topiramate: (Moderate) Topiramate is a carbonic anhydrase inhibitor. Concurrent use of topiramate with non-potassium sparing diuretics (e.g., loop diuretics) may potentiate the potassium-wasting action of these diuretics. Monitor baseline and periodic potassium concentrations during coadministration.
    Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Phenylephrine; Promethazine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
    Pimozide: (Major) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Use of pimozide and medications known to cause electrolyte imbalance may increase the risk of QT prolongation. Therefore, caution is advisable during concurrent use of pimozide and loop diuretics. According to the manufacturer, potassium deficiencies should be correctly prior to treatment with pimozide and normalized potassium levels should be maintained during treatment.
    Pioglitazone: (Moderate) Loop diuretics can decrease the hypoglycemic effects of antidiabetic agents by producing an increase in blood glucose concentrations. Patients receiving antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary.
    Piperacillin: (Minor) Ethacrynic acid 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) Ethacrynic acid 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.
    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) There have been rare reports of generalized tonic-clonic seizures associated with electrolyte abnormalities in patients using polyethylene glycol colon preparation products. In addition, there have been rare reports of serious arrhythmias associated with the use of ionic osmotic laxative products for bowel preparation. Some of these events are associated with electrolyte imbalance. Therefore, polyethylene glycol; electrolytes preparations should be used with caution in patients using concomitant medications that increase the risk of electrolyte abnormalities such as loop diuretics.
    Polyethylene Glycol; Electrolytes: (Moderate) There have been rare reports of generalized tonic-clonic seizures associated with electrolyte abnormalities in patients using polyethylene glycol colon preparation products. In addition, there have been rare reports of serious arrhythmias associated with the use of ionic osmotic laxative products for bowel preparation. Some of these events are associated with electrolyte imbalance. Therefore, polyethylene glycol; electrolytes preparations should be used with caution in patients using concomitant medications that increase the risk of electrolyte abnormalities such as loop diuretics. (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) There have been rare reports of generalized tonic-clonic seizures associated with electrolyte abnormalities in patients using polyethylene glycol colon preparation products. In addition, there have been rare reports of serious arrhythmias associated with the use of ionic osmotic laxative products for bowel preparation. Some of these events are associated with electrolyte imbalance. Therefore, polyethylene glycol; electrolytes preparations should be used with caution in patients using concomitant medications that increase the risk of electrolyte abnormalities such as loop diuretics.
    Polymyxin B: (Moderate) Systemic polymyxin B is nephrotoxic and should be used cautiously with loop diuretics, which may cause azotemia and may increase the risk for renal toxicity when coadministered. Close monitoring of renal status and for drug toxicity is recommended. Diminishing urine output and a rising BUN are indications to discontinue systemic polymyxin B therapy.
    Pramlintide: (Minor) Loop diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between these drugs and all antidiabetic agents. Monitor patient for diabetic control.
    Prazosin: (Moderate) Prazosin is well-known to produce a 'first-dose' phenomenon. Some patients develop significant hypotension shortly after administration of the first dose. The first dose response (acute postural hypotension) of prazosin may be exaggerated in patients who are receiving beta-adrenergic blockers, diuretics, or other antihypertensive agents. Concomitant administration of prazosin with other antihypertensive agents is not prohibited, however. This can be therapeutically advantageous, but lower dosages of each agent should be used.
    Prednisolone: (Moderate) Corticosteroids may accentuate the electrolyte loss associated with diuretic therapy resulting in hypokalemia and/or hypomagnesemia. While glucocorticoids with mineralocorticoid activity (e.g., cortisone, hydrocortisone) can cause sodium and fluid retention. Close monitoring of electrolytes should occur in patients receiving these drugs concomitantly.
    Prednisone: (Moderate) Corticosteroids may accentuate the electrolyte loss associated with diuretic therapy resulting in hypokalemia and/or hypomagnesemia. While glucocorticoids with mineralocorticoid activity (e.g., cortisone, hydrocortisone) can cause sodium and fluid retention. Close monitoring of electrolytes should occur in patients receiving these drugs concomitantly.
    Probenecid: (Moderate) Probenecid has uricosuric actions. Ethacrynic acid can also cause hyperuricemia. Although this effect represents a pharmacodynamic interaction, dosage adjustments of probenecid may be necessary if ethacrynic acid is administered to patients being treated with 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.
    Propofol: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
    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.
    Quetiapine: (Major) QT prolongation has occurred during concurrent use of quetiapine and medications known to cause electrolyte imbalance. Therefore, caution is advisable during concurrent use of quetiapine and loop diuretics.
    Quinapril: (Moderate) Coadministration of loop diuretics and Angiotensin-converting enzyme inhibitors (ACE inhibitors) 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.
    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: (Moderate) Coadministration of loop diuretics and Angiotensin-converting enzyme inhibitors (ACE inhibitors) 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.
    Rapacuronium: (Moderate) Furosemide-induced hypokalemia can potentiate neuromuscular blockade with nondepolarizing neuromuscular blockers. In addition, furosemide may antagonize the skeletal muscle relaxing effect of tubocurarine and can potentiate neuromuscular blockade following succinylcholine administration.
    Rasagiline: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Repaglinide: (Minor) Loop diuretics have been associated with hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between loop diuretics and all antidiabetic agents. Monitor for a loss of diabetic control.
    Risperidone: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
    Rocuronium: (Moderate) Furosemide-induced hypokalemia can potentiate neuromuscular blockade with nondepolarizing neuromuscular blockers. In addition, furosemide may antagonize the skeletal muscle relaxing effect of tubocurarine and can potentiate neuromuscular blockade following succinylcholine administration.
    Rofecoxib: (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.
    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.
    Selegiline: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Senna: (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.
    Serotonin norepinephrine reuptake inhibitors: (Moderate) Patients receiving a diuretic during treatment with venlafaxine may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH may occur during therapy with SNRIs, including venlafaxine. Cases involving serum sodium levels lower than 110 mmol/l have been reported. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of the SNRI should be considered in patients who develop symptomatic hyponatremia.
    Sertraline: (Moderate) Patients receiving a diuretic during treatment with sertraline may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/l have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of sertraline should be considered in patients who develop symptomatic hyponatremia.
    Sevoflurane: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Silodosin: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Sodium Phosphate Monobasic Monohydrate; Sodium Phosphate Dibasic Anhydrous: (Moderate) Concomitant use of medicines with potential to alter renal perfusion or function such as diuretics, may increase the risk of acute phosphate nephropathy in patients receiving sodium phosphate monobasic monohydrate; sodium phosphate dibasic anhydrous. 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.
    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) Furosemide-induced hypokalemia can potentiate neuromuscular blockade with nondepolarizing neuromuscular blockers. In addition, furosemide may antagonize the skeletal muscle relaxing effect of tubocurarine and can potentiate neuromuscular blockade following succinylcholine administration.
    Sulfinpyrazone: (Minor) Because ethacrynic acid can cause hyperuricemia, it may counteract the uricosuric effects of sulfinpyrazone. Dosage adjustments of sulfinpyrazone may be necessary if these agents are administered concurrently to patients with gout.
    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.
    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.
    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) Concomitant use of a thiazide diuretiic, or the related drug metolazone, with a loop diuretic can cause additive electrolyte and fluid loss. In patients with creatinine clearances > 30 ml/min, the combinations may also lead to profound fluid and electrolyte loss in some patients. Thus, use cautiously and with monitoring of renal function, blood pressure, cardiac status, electrolytes (especially potassium), and monitor the clinical response for the condition treated.
    Thiopental: (Moderate) Concurrent use of thiopental and alpha-blockers or antihypertensive agents increases the risk of developing hypotension.
    Thiothixene: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Ticarcillin: (Minor) Ethacrynic acid 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.
    Ticarcillin; Clavulanic Acid: (Minor) Ethacrynic acid 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.
    Tizanidine: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
    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).
    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 these drugs are used together. Coadministration of tolvaptan and loop diuretics increases the risk of too rapid correction of serum sodium.
    Topiramate: (Moderate) Topiramate is a carbonic anhydrase inhibitor. Concurrent use of topiramate with non-potassium sparing diuretics (e.g., loop diuretics) may potentiate the potassium-wasting action of these diuretics. Monitor baseline and periodic potassium concentrations during coadministration.
    Trandolapril: (Moderate) Coadministration of loop diuretics and Angiotensin-converting enzyme inhibitors (ACE inhibitors) 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.
    Trandolapril; Verapamil: (Moderate) Coadministration of loop diuretics and Angiotensin-converting enzyme inhibitors (ACE inhibitors) 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.
    Tranylcypromine: (Severe) The use of hypotensive agents and tranylcypromine is contraindicated by the manufacturer of tranylcypromine because the effects of hypotensive agents may be markedly potentiated.
    Trazodone: (Minor) Due to additive hypotensive effects, patients receiving antihypertensive agents concurrently with trazodone may have excessive hypotension. Decreased dosage of the antihypertensive agent may be required when given with trazodone.
    Triamcinolone: (Moderate) Corticosteroids may accentuate the electrolyte loss associated with diuretic therapy resulting in hypokalemia and/or hypomagnesemia. While glucocorticoids with mineralocorticoid activity (e.g., cortisone, hydrocortisone) can cause sodium and fluid retention. Close monitoring of electrolytes should occur in patients receiving these drugs concomitantly.
    Trospium: (Minor) Diuretics can increase urinary frequency, which may aggravate bladder symptoms.
    Tubocurarine: (Moderate) Furosemide-induced hypokalemia can potentiate neuromuscular blockade with nondepolarizing neuromuscular blockers. In addition, furosemide may antagonize the skeletal muscle relaxing effect of tubocurarine and can potentiate neuromuscular blockade following succinylcholine administration.
    Valdecoxib: (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.
    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.
    Vancomycin: (Major) Vancomycin should be used cautiously with other ototoxic drugs such as ethacrynic acid.
    Vecuronium: (Moderate) Furosemide-induced hypokalemia can potentiate neuromuscular blockade with nondepolarizing neuromuscular blockers. In addition, furosemide may antagonize the skeletal muscle relaxing effect of tubocurarine and can potentiate neuromuscular blockade following succinylcholine administration.
    Venlafaxine: (Moderate) Patients receiving a diuretic during treatment with venlafaxine may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH may occur during therapy with SNRIs, including venlafaxine. Cases involving serum sodium levels lower than 110 mmol/l have been reported. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of the SNRI should be considered in patients who develop symptomatic hyponatremia.
    Vilazodone: (Moderate) Patients receiving vilazodone with medications known to cause hyponatremia, such as diuretics, may be at increased risk of developing hyponatremia. Hyponatremia has occurred in association with the use of antidepressants such as selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), and mirtazapine. Hyponatremia may manifest as headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness which may result in falls. Severe manifestations include hallucinations, syncope, seizure, coma, respiratory arrest, and death. Symptomatic hyponatremia may require discontinuation of vilazodone, as well as implementation of the appropriate medical interventions.
    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.
    Warfarin: (Major) Although data are very limited, there have been reports of increased hypoprothrombinemia when ethacrynic acid was administered to patients receiving warfarin. Per the prescribing information for warfarin sodium, concomitant use of diuretics and warfarin may result in an increased or decreased PT/INR. According to the manufacturer for ethacrynic acid, ethacrynic acid has been shown to displace warfarin from plasma protein; a reduction in the usual anticoagulant dosage may be required in patients receiving both drugs. Patients should be monitored for changes in the INR when either of these drugs is initiated or discontinued, or if the dosage is changed.
    Yohimbine: (Moderate) Yohimbine can increase blood pressure and therefore can antagonize the therapeutic action of antihypertensive agents. Use with particular caution in hypertensive patients with high or uncontrolled BP.
    Ziconotide: (Moderate) Patients taking diuretics with ziconotide may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, consideration of diuretic cessation is warranted in addition to ziconotide discontinuation.
    Ziprasidone: (Minor) Monitor of 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

    Ethacrynic acid is classified as FDA pregnancy risk category B. There are no adequate studies available on the safety of ethacrynic acid therapy during pregnancy, so the drug should be administered to pregnant women only when absolutely necessary. Diuretics are generally not recommended for the treatment of pregnancy-induced hypertension (preeclampsia, eclampsia) since they do not alter the course of toxemia and may exacerbate maternal hypovolemia associated with this condition.

    According to the manufacturer, it is not known whether ethacrynic acid is excreted in human milk. The manufacturer recommends that a decision be made either to discontinue breast-feeding or to discontinue the drug, taking into account the importance of the drug to the mother. Diuretics, such as ethacrynic acid, may suppress lactation as a result of intense diuresis. Of note, the use of bendroflumethiazide, chlorthalidone, chlorothiazide, and hydrochlorothiazide is considered to be usually compatible with breast-feeding by the American Academy of Pediatrics (AAP) due to lack of noted adverse effects on the nursing infant. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    Ethacrynic acid is a loop diuretic. It differs structurally (i.e., it is not a sulfonamide) from furosemide, and it is more potent than furosemide on a weight basis. Similar to other loop diuretics, ethacrynic acid primarily acts to inhibit the reabsorption of sodium and chloride in the ascending limb of the loop of Henle. Loop diuretics interfere with the chloride-binding of the Na+/K+/2Cl- cotransport system, altering electrolyte transfer in the proximal tubule. A profound diuresis results from the increased urinary excretion of sodium, chloride, potassium, and hydrogen ions. In addition, ethacrynic acid increases the excretion of calcium, magnesium, bicarbonate, ammonium, and phosphate. Aldosterone production is stimulated following diuresis and volume contraction, resulting in increased sodium resorption and increased potassium and hydrogen excretion. Excessive loss of these electrolytes can lead to metabolic alkalosis. Unlike other loop diuretics, ethacrynic acid contains a beta-unsaturated ketone moiety, and was originally synthesized to mimic the sulfhydryl reactivity of the mercurial diuretics. The increased propensity of ethacrynic acid to bind to renal protein sulfhydryl groups may contribute to its diuretic actions by inhibiting sulfhydryl-catalyzed enzyme systems. Ethacrynic acid is not an aldosterone antagonist, and it does not affect carbonic anhydrase activity.
     
    Ethacrynic acid produces greater diuresis and electrolyte loss than do other diuretics (except furosemide or bumetanide), and its effectiveness is independent of the acid-base status of the patient. It has little to no effect on renal blood flow or the glomerular filtration rate; however, rapid or excessive diuresis can produce a decrease in the glomerular filtration rate. Initially, diuretics lower blood pressure by decreasing cardiac output and reducing plasma and extracellular fluid volume. Cardiac output eventually returns to normal, but peripheral resistance is reduced, resulting in lower blood pressure. In general, diuretics worsen glucose tolerance and exert detrimental effects on the lipid profile.

    PHARMACOKINETICS

    Ethacrynic acid is administered orally and intravenously.  Ethacrynic acid concentrates in the liver, and it is not known whether it crosses the placenta or is distributed in breast milk. Ethacrynic acid undergoes hepatic metabolism to an active metabolite, with 30—65% of a dose excreted in the urine and 35—40% excreted in the bile. The urinary excretion of ethacrynic acid increases as urinary pH increases. Some tubular secretion occurs since ethacrynic acid clearance is reduced by probenecid. Increased doses may be needed in patients with renal impairment to achieve the desired response.

    Oral Route

    Ethacrynic acid is absorbed rapidly following an oral dose. Bioavailability is approximately 100%, with onset of diuresis occurring within 30 minutes after oral administration. Peak effects occur at around 2 hours, and the duration of action is approximately 6—8 hours.

    Intravenous Route

    Following IV administration of ethacrynic acid, the onset of action is 5 minutes, with peak effects occurring within 15—30 minutes. The duration of action is approximately 2 hours.