Demadex

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Demadex

Classes

Loop Diuretics

Administration
Oral Administration

May be administered orally without regard to meals.
NOTE: The oral bioavailability of torsemide is sufficiently high to allow for 1:1 equivalency between the oral and intravenous dosage forms.

Injectable Administration

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

Intravenous Administration

For intravenous use only. Torsemide injection should be administered either slowly as an IV bolus or as a continuous IV infusion.
NOTE: The bioavailability of torsemide allows for 1:1 equivalency between the oral and intravenous dosage forms. Based on clinical data of diuretic potency, 10 to 20 mg IV of torsemide is approximately equivalent to 40 mg IV of furosemide.
Ampuls are single-use containers. Discard any unused portion after opening.
 
Intravenous Bolus Injection:
No dilution necessary if given as a slow IV injection.
Administer slowly over a period of 2 minutes.
If administered through an IV line, flush the line with 0.9% Sodium Chloride Injection, USP (NS) before and after administration. The torsemide injection is formulated above pH 8.3. Flushing the line is recommended to avoid the potential for incompatibilities caused by differences in pH which could be indicated by color change, haziness, or the formation of a precipitate in the solution.
 
Continuous Intravenous Infusion:
If administered through an IV line, flush the line with 0.9% Sodium Chloride Injection, USP (NS) before and after administration. The torsemide injection is formulated above pH 8.3. Flushing the line is recommended to avoid the potential for incompatibilities caused by differences in pH which could be indicated by color change, haziness, or the formation of a precipitate in the solution.
If administered as a continuous infusion, stability has been demonstrated through 24 hours at room temperature of 15 to 30 degrees C (59 to 86 degrees F), in plastic containers, for the following fluids and concentrations:
200 mg Torsemide (10 mg/mL) added to: 250 mL D5W (0.8 mg/ml), 250 mL 0.9% Sodium Chloride (NS) (0.8 mg/ml), or 500 mL 0.45% Sodium Chloride (0.4 mg/ml).
50 mg Torsemide (10 mg/mL) added to: 500 mL D5W (0.1 mg/ml), 500 mL 0.9% Sodium Chloride (NS) (0.1 mg/ml), or 500 mL 0.45% Sodium Chloride (0.1 mg/ml).

Adverse Reactions
Severe

hearing loss / Delayed / Incidence not known
ototoxicity / Delayed / Incidence not known
pancreatitis / Delayed / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known
visual impairment / Early / Incidence not known
renal failure / Delayed / Incidence not known
azotemia / Delayed / Incidence not known

Moderate

hypokalemia / Delayed / 1.5-1.5
hyponatremia / Delayed / Incidence not known
hypomagnesemia / Delayed / Incidence not known
hypocalcemia / Delayed / Incidence not known
metabolic alkalosis / Delayed / Incidence not known
hypochloremia / Delayed / Incidence not known
hyperuricemia / Delayed / Incidence not known
gout / Delayed / Incidence not known
hyperglycemia / Delayed / Incidence not known
leukopenia / Delayed / Incidence not known
thrombocytopenia / Delayed / Incidence not known
anemia / Delayed / Incidence not known
confusion / Early / Incidence not known
urinary retention / Early / Incidence not known
elevated hepatic enzymes / Delayed / Incidence not known
hypovolemia / Early / Incidence not known
hypotension / Rapid / Incidence not known
dehydration / Delayed / Incidence not known

Mild

polyuria / Early / 6.7-15.0
increased urinary frequency / Early / 6.7-15.0
tinnitus / Delayed / Incidence not known
anorexia / Delayed / Incidence not known
abdominal pain / Early / Incidence not known
photosensitivity / Delayed / Incidence not known
pruritus / Rapid / Incidence not known
paresthesias / Delayed / Incidence not known

Common Brand Names

Demadex, SOAANZ

Dea Class

Rx

Description

Oral loop diuretic
Used for hypertension, and for edema associated with heart failure, chronic renal failure, and hepatic cirrhosis
Twice as potent as furosemide with a higher bioavailability and longer half-life; may have less pronounced effect on potassium excretion

Dosage And Indications
For the treatment of edema associated with heart failure or chronic renal disease (renal impairment). For edema associated with congestive heart failure. Oral dosage (Demadex and generic equivalents) Adults

10 to 20 mg PO once daily, initially. Double the dose as needed until the desired diuretic effect is attained. Doses more than 200 mg have not been adequately studied. Guidelines recommend adding a loop diuretic to standard therapy for reduced ejection fraction heart failure (HFrEF) patients with volume overload. Diuretics should also be used in preserved ejection fraction heart failure (HFpEF).

Oral dosage (Soaanz) Adults

20 mg PO once daily, initially. Double the dose as needed until the desired diuretic effect is attained. Doses more than 200 mg have not been adequately studied. Guidelines recommend adding a loop diuretic to standard therapy for reduced ejection fraction heart failure (HFrEF) patients with volume overload. Diuretics should also be used in preserved ejection fraction heart failure (HFpEF).

For edema associated with chronic renal disease (renal impairment). Oral dosage (Demadex and generic equivalents) Adults

10 to 20 mg PO once daily, initially. Double the dose as needed until the desired diuretic effect is attained. Doses more than 200 mg have not been adequately studied.

Oral dosage (Soaanz) Adults

20 mg PO once daily, initially. Double the dose as needed until the desired diuretic effect is attained. Doses more than 200 mg have not been adequately studied.

For the treatment of ascites and edema due to hepatic cirrhosis. Oral dosage (Demadex and generic equivalents) Adults

Initially, 5 to 10 mg PO once daily. If needed, titrate upwards by doubling the dose up to 40 mg PO to achieve a satisfactory diuretic response. Doses greater than 40 mg have not been evaluated in patients with hepatic cirrhosis. Chronic use in hepatic disease has not been evaluated. To prevent hypokalemia and metabolic alkalosis, an aldosterone antagonist or potassium-sparing drug should be used concomitantly.

For the treatment of hypertension. Oral dosage (Demadex and generic equivalents) Adults

5 mg PO once daily, initially. May increase dose to 10 mg PO once daily after 4 to 6 weeks if further control is needed. Max: 10 mg/day.

Dosing Considerations
Hepatic Impairment

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

Renal Impairment

No dosage adjustment is needed; however, high doses may be effective in patients with end-stage renal disease.
 
Intermittent hemodialysis
Torsemide is not removed by hemodialysis; no dosage adjustment is needed.

Drug Interactions

Acarbose: (Minor) Loop diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Acetaminophen; Codeine: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and codeine; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Acetaminophen; Dichloralphenazone; Isometheptene: (Major) Isometheptene has sympathomimetic properties. Patients taking antihypertensive agents may need to have their therapy modified. Careful blood pressure monitoring is recommended.
Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Acetaminophen; Hydrocodone: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and hydrocodone; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Acetaminophen; 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.
Acetaminophen; Oxycodone: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and oxycodone; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Acetaminophen; 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.
Albuterol; Budesonide: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
Alemtuzumab: (Moderate) Alemtuzumab may cause hypotension. Careful monitoring of blood pressure and hypotensive symptoms is recommended especially in patients with ischemic heart disease and in patients on antihypertensive agents.
Alendronate: (Moderate) When the intravenous formulation of alendronate is used for the treatment of hypercalcemia of malignancy, combination therapy with loop diuretics should be used with caution in order to avoid hypocalcemia. In patients with hypercalcemia of malignancy, the initial treatment typically includes the use of loop diuretics, in combination with saline hydration, however, diuretic therapy should not be employed prior to correction of hypovolemia and dehydration.
Alendronate; Cholecalciferol: (Moderate) When the intravenous formulation of alendronate is used for the treatment of hypercalcemia of malignancy, combination therapy with loop diuretics should be used with caution in order to avoid hypocalcemia. In patients with hypercalcemia of malignancy, the initial treatment typically includes the use of loop diuretics, in combination with saline hydration, however, diuretic therapy should not be employed prior to correction of hypovolemia and dehydration.
Alfentanil: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when a loop diuretic is administered with alfentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Aliskiren: (Moderate) Aliskiren can enhance the effects of loop-diuretics on blood pressure if given concomitantly. This additive effect may be desirable, but dosages must be adjusted accordingly. Patients with hyponatremia or hypovolemia may also develop reversible renal insufficiency. When aliskiren is administered in combination with furosemide, the AUC and Cmax of furosemide are reduced by approximately 30% and 50%, respectively; the pharmacokinetics of aliskiren are not affected. Patients should be monitored for loss of effect of furosemide when aliskiren is initiated. Blood pressure and electrolytes should be routinely monitored.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Aliskiren can enhance the effects of loop-diuretics on blood pressure if given concomitantly. This additive effect may be desirable, but dosages must be adjusted accordingly. Patients with hyponatremia or hypovolemia may also develop reversible renal insufficiency. When aliskiren is administered in combination with furosemide, the AUC and Cmax of furosemide are reduced by approximately 30% and 50%, respectively; the pharmacokinetics of aliskiren are not affected. Patients should be monitored for loss of effect of furosemide when aliskiren is initiated. Blood pressure and electrolytes should be routinely monitored. (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
Alogliptin: (Minor) Although the incidence is low, hyperglycemia has been detected during torsemide therapy, probably due to diuretic-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between torsemide and all antidiabetic agents, including alogliptin. Patients on antidiabetic medications should monitor their blood glucose regularly if torsemide is prescribed.
Alogliptin; Metformin: (Minor) Although the incidence is low, hyperglycemia has been detected during torsemide therapy, probably due to diuretic-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between torsemide and all antidiabetic agents, including alogliptin. Patients on antidiabetic medications should monitor their blood glucose regularly if torsemide is prescribed. (Minor) Hyperglycemia has been detected during torsemide therapy, but the incidence is low. Because of this, a potential pharmacodynamic interaction exists between torsemide and all antidiabetic agents, including metformin. Monitor blood glucose.
Alogliptin; Pioglitazone: (Minor) Although the incidence is low, hyperglycemia has been detected during torsemide therapy, probably due to diuretic-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between torsemide and all antidiabetic agents, including alogliptin. Patients on antidiabetic medications should monitor their blood glucose regularly if torsemide is prescribed. (Minor) Hyperglycemia has been detected during torsemide therapy, but the incidence is low. Patients on antidiabetic medications should monitor their blood glucose regularly if torsemide is prescribed.
Alpha-glucosidase Inhibitors: (Minor) Loop diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely.
Alprostadil: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as loop diuretics, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
Aluminum Hydroxide; Magnesium Hydroxide: (Moderate) Monitor potassium concentration before and during concomitant laxative, such as magnesium hydroxide, and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary.
Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Moderate) Monitor potassium concentration before and during concomitant laxative, such as magnesium hydroxide, and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary.
Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
Aminoglycosides: (Moderate) The risk of ototoxicity or nephrotoxicity secondary to aminoglycosides may be increased by the addition of concomitant therapies with similar side effects, including loop diuretics. If loop diuretics and aminoglycosides are used together, it would be prudent to monitor renal function parameters, serum electrolytes, and serum aminoglycoside concentrations during therapy. Audiologic monitoring may be advisable during high dose therapy or therapy of long duration, when hearing loss is suspected, or in selected risk groups (e.g., neonates).
Amiodarone: (Moderate) Monitor serum electrolytes if coadministration of bumetanide and amiodarone is necessary. Bumetanide therapy may cause electrolyte abnormalities (i.e., hypokalemia, hypomagnesemia) which may exaggerate the degree of QTc prolongation and increase the potential for torsade de pointes. In addition, monitor the diuretic effect and blood pressure if torsemide and amiodarone are administered together. The torsemide dose may need to be reduced. The concomitant use of torsemide and amiodarone can decrease torsemide clearance and increase torsemide plasma concentrations. Torsemide is a substrate of CYP2C9; amiodarone inhibits CYP2C9.
Amlodipine; Benazepril: (Major) Discontinue the loop diuretic prior to starting benazepril, if possible, or start benazepril at the lower dose of 5 mg/day. Monitor blood pressure and renal function during concomitant use, particularly when doses are increased. Concomitant use may increase the risk for hypotension or renal failure.
Amlodipine; Celecoxib: (Moderate) If celecoxib (an NSAID) and torsemide (a diuretic) are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy; side effects from celecoxib may also increase. The concomitant use of celecoxib, a sensitive substrate of CYP2C9, and torsemide, a CYP2C9 inhibitor, may result in increased plasma concentrations of celecoxib. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain.
Amlodipine; Olmesartan: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative.
Amlodipine; Valsartan: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative. (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
Amobarbital: (Moderate) Concurrent use of amobarbital with antihypertensive agents may lead to hypotension. Monitor for decreases in blood pressure during times of coadministration.
Amoxicillin; Clarithromycin; Omeprazole: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and loop diuretic use due to risk for hypomagnesemia.
Amphetamine: (Minor) Amphetamine and Dextroamphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as loop diuretics. Close monitoring of blood pressure is advised.
Amphetamine; Dextroamphetamine Salts: (Minor) Amphetamine and Dextroamphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as loop diuretics. Close monitoring of blood pressure is advised.
Amphetamine; Dextroamphetamine: (Minor) Amphetamine and Dextroamphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as loop diuretics. Close monitoring of blood pressure is advised.
Amphotericin B 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.
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.
Apalutamide: (Moderate) Monitor diuretic effect and blood pressure if coadministration of torsemide with apalutamide is necessary. Torsemide is a CYP2C9 substrate and apalutamide is a CYP2C9 inducer. Concomitant use of CYP2C9 inducers increases torsemide clearance and decreases torsemide plasma concentrations.
Apomorphine: (Moderate) Use of loop diuretics and apomorphine together can increase the hypotensive effects of apomorphine. Monitor blood pressure regularly during use of this combination.
Apraclonidine: (Minor) Alpha blockers as a class may reduce heart rate and blood pressure. While no specific drug interactions have been identified with systemic agents and apraclonidine during clinical trials, it is theoretically possible that additive blood pressure reductions could occur when apraclonidine is combined with the use of antihypertensive agents. Patients using cardiovascular drugs concomitantly with apraclonidine should have their pulse and blood pressure monitored periodically.
Aprepitant, Fosaprepitant: (Minor) Use caution if torsemide and aprepitant are used concurrently and monitor for a possible decrease in the efficacy of torsemide. After administration, fosaprepitant is rapidly converted to aprepitant and shares the same drug interactions. Torsemide is a CYP2C9 substrate and aprepitant is a CYP2C9 inducer. Administration of a CYP2C9 substrate, tolbutamide, on days 1, 4, 8, and 15 with a 3-day regimen of oral aprepitant (125 mg/80 mg/80 mg) decreased the tolbutamide AUC by 23% on day 4, 28% on day 8, and 15% on day 15. The AUC of tolbutamide was decreased by 8% on day 2, 16% on day 4, 15% on day 8, and 10% on day 15 when given prior to oral administration of aprepitant 40 mg on day 1, and on days 2, 4, 8, and 15. The effects of aprepitant on tolbutamide were not considered significant. When a 3-day regimen of aprepitant (125 mg/80 mg/80 mg) given to healthy patients on stabilized chronic warfarin therapy (another CYP2C9 substrate), a 34% decrease in S-warfarin trough concentrations was noted, accompanied by a 14% decrease in the INR at five days after completion of aprepitant.
Aripiprazole: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
Arsenic Trioxide: (Moderate) Use caution when using arsenic trioxide concomitantly with loop diuretics, as these can cause electrolyte abnormalities, which can increase the risk of QT prolongation.
Articaine; Epinephrine: (Moderate) Monitor blood pressure, heart rate, and serum potassium during concomitant epinephrine and loop diuretic use. Loop diuretics may antagonize the pressor effects and potentiate the arrhythmogenic and hypokalemic effects of epinephrine.
Asenapine: (Moderate) Secondary to alpha-blockade, asenapine can produce vasodilation that may result in additive effects during concurrent use of antihypertensive agents. The potential reduction in blood pressure can precipitate orthostatic hypotension and associated dizziness, tachycardia, and syncope. If concurrent use of asenapine and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and codeine; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Aspirin, ASA; Omeprazole: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and loop diuretic use due to risk for hypomagnesemia.
Aspirin, ASA; Oxycodone: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and oxycodone; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Atenolol; Chlorthalidone: (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
Atracurium: (Moderate) Concomitant use of neuromuscular blockers and loop diuretics may prolong neuromuscular blockade, possibly due to hypokalemia or alterations in potassium concentrations across the end-plate membrane.
Azelastine; Fluticasone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
Azilsartan: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative.
Azilsartan; Chlorthalidone: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative. (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
Bacitracin: (Minor) Additive nephrotoxicity may occur with concurrent use of systemic bacitracin and other nephrotoxic agents. When possible, avoid concomitant administration of systemic bacitracin and other nephrotoxic drugs such as loop diuretics. Topical administration of any preparation containing bacitracin, especially when applied to large surface areas, also should not be given with other drugs that have a nephrotoxic potential. (Minor) Additive nephrotoxicity may occur with concurrent use of these medicines. When possible, avoid concomitant administration of systemic bacitracin and loop diuretics. Use of topically administrated preparations containing bacitracin, especially when applied to large surface areas, may have additive nephrotoxic potential with loop diuretics.
Bacitracin; Hydrocortisone; Neomycin; Polymyxin B: (Minor) Additive nephrotoxicity may occur with concurrent use of systemic bacitracin and other nephrotoxic agents. When possible, avoid concomitant administration of systemic bacitracin and other nephrotoxic drugs such as loop diuretics. Topical administration of any preparation containing bacitracin, especially when applied to large surface areas, also should not be given with other drugs that have a nephrotoxic potential.
Bacitracin; Polymyxin B: (Minor) Additive nephrotoxicity may occur with concurrent use of systemic bacitracin and other nephrotoxic agents. When possible, avoid concomitant administration of systemic bacitracin and other nephrotoxic drugs such as loop diuretics. Topical administration of any preparation containing bacitracin, especially when applied to large surface areas, also should not be given with other drugs that have a nephrotoxic potential.
Baclofen: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
Beclomethasone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
Belladonna; Opium: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when loop diuretics are administered with opium. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Benazepril: (Major) Discontinue the loop diuretic prior to starting benazepril, if possible, or start benazepril at the lower dose of 5 mg/day. Monitor blood pressure and renal function during concomitant use, particularly when doses are increased. Concomitant use may increase the risk for hypotension or renal failure.
Benazepril; Hydrochlorothiazide, HCTZ: (Major) Discontinue the loop diuretic prior to starting benazepril, if possible, or start benazepril at the lower dose of 5 mg/day. Monitor blood pressure and renal function during concomitant use, particularly when doses are increased. Concomitant use may increase the risk for hypotension or renal failure. (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
Benzhydrocodone; Acetaminophen: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when loop diuretics are administered with benzhydrocodone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Benzphetamine: (Minor) Benzphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as loop diuretics. Close monitoring of blood pressure is advised.
Beta-agonists: (Moderate) Use beta-agonists and loop diuretics with caution due to risk for ECG changes and/or hypokalemia. The ECG changes and/or hypokalemia that may result from administration of loop diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded.
Betamethasone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
Bisacodyl: (Moderate) Loop diuretics may increase the risk of hypokalemia especially in patients receiving prolonged therapy with laxatives. Monitor serum potassium levels to determine the need for potassium supplementation and/or alteration in drug therapy.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
Brexpiprazole: (Moderate) Due to brexpiprazole's antagonism at alpha 1-adrenergic receptors, the drug may enhance the hypotensive effects of alpha-blockers and other antihypertensive agents.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Brompheniramine; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Brompheniramine; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Budesonide: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
Budesonide; Formoterol: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
Bupivacaine; Epinephrine: (Moderate) Monitor blood pressure, heart rate, and serum potassium during concomitant epinephrine and loop diuretic use. Loop diuretics may antagonize the pressor effects and potentiate the arrhythmogenic and hypokalemic effects of epinephrine.
Bupivacaine; Meloxicam: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain.
Buprenorphine: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and buprenorphine; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Buprenorphine; Naloxone: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and buprenorphine; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and codeine; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and codeine; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Cabergoline: (Moderate) Cabergoline should be used cautiously with antihypertensive agents, including loop diuretics. Cabergoline has been associated with hypotension. Initial doses of cabergoline higher than 1 mg may produce orthostatic hypotension. It may be advisable to monitor blood pressure.
Calcium Phosphate, Supersaturated: (Moderate) Concomitant use of medicines with potential to alter renal perfusion or function such as diuretics, may increase the risk of acute phosphate nephropathy in patients receiving sodium phosphate monobasic monohydrate; sodium phosphate dibasic anhydrous. In addition, loop diuretics may increase the risk of hypokalemia especially in patients receiving prolonged therapy with laxatives. Monitor serum potassium levels to determine the need for potassium supplementation and/or alteration in drug therapy.
Canagliflozin: (Major) Assess and correct volume status before initiating canagliflozin in persons receiving concomitant loop diuretics. Monitor for signs and symptoms of volume depletion and loss of glycemic control after initiating therapy due to increased risk for volume depletion or hypotension and loss of blood glucose control. Persons receiving loop diuretics may be at increased risk for volume depletion or hypotension with concomitant canagliflozin therapy. Loop diuretics tend to produce hyperglycemia and may lead to loss of glycemic control.
Canagliflozin; Metformin: (Major) Assess and correct volume status before initiating canagliflozin in persons receiving concomitant loop diuretics. Monitor for signs and symptoms of volume depletion and loss of glycemic control after initiating therapy due to increased risk for volume depletion or hypotension and loss of blood glucose control. Persons receiving loop diuretics may be at increased risk for volume depletion or hypotension with concomitant canagliflozin therapy. Loop diuretics tend to produce hyperglycemia and may lead to loss of glycemic control. (Minor) Hyperglycemia has been detected during torsemide therapy, but the incidence is low. Because of this, a potential pharmacodynamic interaction exists between torsemide and all antidiabetic agents, including metformin. Monitor blood glucose.
Candesartan: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative.
Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative. (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
Cannabidiol: (Moderate) Consider a dose reduction of torsemide as clinically appropriate, if adverse reactions occur when administered with cannabidiol. Increased torsemide exposure is possible. Torsemide is a CYP2C9 substrate. In vitro data predicts inhibition of CYP2C9 by cannabidiol potentially resulting in clinically significant interactions.
Capecitabine: (Moderate) Monitor diuretic effect and blood pressure if coadministration of torsemide with capecitabine is necessary; adjust the dose of torsemide if clinically appropriate. Torsemide is a CYP2C9 substrate and capecitabine is a weak CYP2C9 inhibitor. Concomitant use can decrease torsemide clearance and increase torsemide plasma concentrations.
Capreomycin: (Moderate) The risk of ototoxicity or nephrotoxicity secondary to capreomycin may be increased by the addition of concomitant therapies with similar side effects, including loop diuretics. Ototoxicity from furosemide or other loop diuretics, while uncommon, can be a transient or permanent side effect of significance. Ototoxicity is best documented with the loop diuretics ethacrynic acid and furosemide, but may also occur with either bumetanide or torsemide. The exact mechanism by which furosemide or other loop diuretics produce ototoxicity is unknown. Usually, reports indicate that furosemide ototoxicity is associated with rapid injection, severe renal impairment, higher than recommended dosages or infusion rates, or concomitant therapy with aminoglycoside antibiotics, ethacrynic acid, or other ototoxic drugs. If loop diuretics and capreomycin are used together, it would be prudent to monitor renal function parameters, serum electrolytes, and serum aminoglycoside concentrations during therapy. Audiologic monitoring may be advisable during high dose therapy or therapy of long duration, when hearing loss is suspected, or in selected risk groups (e.g., neonates).
Captopril: (Major) Discontinue the loop diuretic prior to starting captopril, if possible, or start captopril at the lower dose of 6.25 or 12.5 mg/day. Monitor blood pressure and renal function during concomitant use, particularly when doses are increased. Concomitant use may increase the risk for hypotension or renal failure.
Captopril; Hydrochlorothiazide, HCTZ: (Major) Discontinue the loop diuretic prior to starting captopril, if possible, or start captopril at the lower dose of 6.25 or 12.5 mg/day. Monitor blood pressure and renal function during concomitant use, particularly when doses are increased. Concomitant use may increase the risk for hypotension or renal failure. (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
Carbidopa; Levodopa: (Moderate) Monitor blood pressure during concomitant levodopa and loop diuretic use due to risk for additive hypotension; a loop diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
Carbidopa; Levodopa; Entacapone: (Moderate) Monitor blood pressure during concomitant levodopa and loop diuretic use due to risk for additive hypotension; a loop diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
Cardiac glycosides: (Moderate) Monitor serum magnesium and potassium during concomitant cardiac glycoside and loop diuretic use. Potassium-depleting diuretics are a major contributing factor to digoxin toxicity.
Cariprazine: (Moderate) Orthostatic vital signs should be monitored in patients who are at risk for hypotension, such as those receiving cariprazine in combination with antihypertensive agents. Atypical antipsychotics may cause orthostatic hypotension and syncope, most commonly during treatment initiation and dosage increases. Patients should be informed about measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning, or rising slowly from a seated position. Consider a cariprazine dose reduction if hypotension occurs.
Castor Oil: (Moderate) Loop diuretics may increase the risk of hypokalemia especially in patients receiving prolonged therapy with laxatives. Monitor serum potassium levels to determine the need for potassium supplementation and/or alteration in drug therapy.
Cefaclor: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
Cefadroxil: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
Cefazolin: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
Cefdinir: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
Cefepime: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
Cefiderocol: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
Cefixime: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
Cefotaxime: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
Cefotetan: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
Cefoxitin: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
Cefpodoxime: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
Cefprozil: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
Ceftaroline: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
Ceftazidime: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
Ceftazidime; Avibactam: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
Ceftolozane; Tazobactam: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
Ceftriaxone: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
Cefuroxime: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
Celecoxib: (Moderate) If celecoxib (an NSAID) and torsemide (a diuretic) are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy; side effects from celecoxib may also increase. The concomitant use of celecoxib, a sensitive substrate of CYP2C9, and torsemide, a CYP2C9 inhibitor, may result in increased plasma concentrations of celecoxib. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain.
Celecoxib; Tramadol: (Moderate) If celecoxib (an NSAID) and torsemide (a diuretic) are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy; side effects from celecoxib may also increase. The concomitant use of celecoxib, a sensitive substrate of CYP2C9, and torsemide, a CYP2C9 inhibitor, may result in increased plasma concentrations of celecoxib. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and tramadol; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Cephalexin: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
Cephalosporins: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
Ceritinib: (Moderate) Monitor diuretic effect and blood pressure if torsemide is used in combination with ceritinib; adjust the dose of torsemide if necessary. Ceritinib is a weak CYP2C9 inhibitor and torsemide is primarily metabolized by CYP2C9.
Cetirizine; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Chloroprocaine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
Chlorothiazide: (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
Chlorpheniramine; Codeine: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and codeine; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Chlorpheniramine; Hydrocodone: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and hydrocodone; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Chlorpheniramine; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Chlorpheniramine; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Chlorthalidone: (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
Chlorthalidone; Clonidine: (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
Cholestyramine: (Minor) Cholestyramine inhibits the oral bioavailability of torsemide. Simultaneous use of torsemide and cholestyramine is not recommended. Stagger the administration times of cholestyramine and oral torsemide by several hours to avoid the possibility of this interaction.
Ciclesonide: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
Cidofovir: (Contraindicated) The administration of cidofovir with another potentially nephrotoxic agent, such as diuretics, is contraindicated. Diuretics should be discontinued at least 7 days prior to beginning cidofovir.
Cisapride: (Major) Cisapride should be used with great caution in patients receiving potassium-wasting diuretic therapies, such as loop diuretics. Drugs that are associated with depletion of electrolytes may cause cisapride-induced cardiac arrhythmias.
Cisatracurium: (Moderate) Concomitant use of neuromuscular blockers and loop diuretics may prolong neuromuscular blockade, possibly due to hypokalemia or alterations in potassium concentrations across the end-plate membrane.
Cisplatin: (Moderate) Closely monitor renal function and audiometric testing if concomitant use of cisplatin and torsemide is necessary. Both cisplatin and torsemide can cause nephrotoxicity and ototoxicity, which may be additive when used together.
Citalopram: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and citalopram use; consider discontinuing citalopram if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Cocaine: (Major) Use of cocaine with antihypertensive agents may increase the antihypertensive effects of the antihypertensive medications or may potentiate cocaine-induced sympathetic stimulation.
Codeine:

(Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and codeine; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Codeine; Guaifenesin: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and codeine; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and codeine; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Codeine; Phenylephrine; Promethazine: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and codeine; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Codeine; Promethazine: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and codeine; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Co-Enzyme Q10, Ubiquinone: (Moderate) Monitor blood pressure during concomitant co-enzyme Q10 (ubiquinone) and loop diuretic use. Concomitant use may result in additive hypotension.
Corticosteroids: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
Corticotropin, ACTH: (Minor) Monitor potassium concentrations during concomitant corticotropin and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticotropin and loop diuretics cause increased renal potassium loss.
Cortisone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
Cosyntropin: (Moderate) Use cosyntropin cautiously in patients receiving diuretics. Cosyntropin may accentuate the electrolyte loss associated with diuretic therapy.
Dapagliflozin: (Moderate) Loop diuretics can decrease the hypoglycemic effects of antidiabetic agents by producing an increase in blood glucose concentrations. Patients receiving dapagliflozin should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary.
Dapagliflozin; Metformin: (Moderate) Loop diuretics can decrease the hypoglycemic effects of antidiabetic agents by producing an increase in blood glucose concentrations. Patients receiving dapagliflozin should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. (Minor) Hyperglycemia has been detected during torsemide therapy, but the incidence is low. Because of this, a potential pharmacodynamic interaction exists between torsemide and all antidiabetic agents, including metformin. Monitor blood glucose.
Dapagliflozin; Saxagliptin: (Moderate) Loop diuretics can decrease the hypoglycemic effects of antidiabetic agents by producing an increase in blood glucose concentrations. Patients receiving dapagliflozin should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. (Minor) 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. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if these drugs are initiated.
Darifenacin: (Minor) Diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Deflazacort: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
Desloratadine; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Desmopressin: (Contraindicated) Desmopressin is contraindicated with concomitant loop diuretic use due to an increased risk of hyponatremia.
Desvenlafaxine: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and serotonin norepinephrine reuptake inhibitor (SNRI) use; consider discontinuing the SNRI if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Dexamethasone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
Dexbrompheniramine; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Dexlansoprazole: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with loop diuretics (furosemide, bumetanide, torsemide, and ethacrynic acid). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
Dextroamphetamine: (Minor) Amphetamine and Dextroamphetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as loop diuretics. Close monitoring of blood pressure is advised.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Dextromethorphan; Quinidine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Diazoxide: (Moderate) Additive hypotensive effects can occur with the concomitant administration of diazoxide with loop diuretics. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly. The manufacturer advises that IV diazoxide should not be administered to patients within 6 hours of receiving other antihypertensive agents.
Dichlorphenamide: (Moderate) Use dichlorphenamide and torsemide together with caution. Dichlorphenamide increases potassium excretion and can cause hypokalemia and should be used cautiously with other drugs that may cause hypokalemia including torsemide. Measure potassium concentrations at baseline and periodically during dichlorphenamide treatment. If hypokalemia occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy.
Diclofenac: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain.
Diclofenac; Misoprostol: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain.
Diethylpropion: (Major) Diethylpropion has vasopressor effects and may limit the benefit of loop diuretics. Although leading drug interaction texts differ in the potential for an interaction between diethylpropion and this group of antihypertensive agents, these effects are likely to be clinically significant and have been described in hypertensive patients on these medications.
Diflunisal: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain.
Digoxin: (Moderate) Monitor serum magnesium and potassium during concomitant cardiac glycoside and loop diuretic use. Potassium-depleting diuretics are a major contributing factor to digoxin toxicity.
Diphenhydramine; Ibuprofen: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain.
Diphenhydramine; Naproxen: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain.
Diphenhydramine; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Dofetilide: (Major) Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs such as loop diuretics increasing the potential for dofetilide-induced torsade de pointes. Potassium levels should be within the normal range prior and during administration of dofetilide.
Dolasetron: (Moderate) Caution is advisable during concurrent use of dolasetron and loop diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with dolasetron.
Droperidol: (Moderate) Caution is advised when using droperidol in combination with loop diuretics which may lead to electrolyte abnormalities, especially hypokalemia or hypomagnesemia, as such abnormalities may increase the risk for QT prolongation or cardiac arrhythmias.
Dulaglutide: (Minor) Loop diuretics, such as bumetanide, furosemide, and torsemide, may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between these drugs and all antidiabetic agents, including incretin mimetics. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if these drugs are initiated.
Duloxetine: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and serotonin norepinephrine reuptake inhibitor (SNRI) use; consider discontinuing the SNRI if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Elexacaftor; tezacaftor; ivacaftor: (Minor) Increased monitoring is recommended if ivacaftor is administered concurrently with CYP2C9 substrates, such as torsemide. In vitro studies showed ivacaftor to be a weak inhibitor of CYP2C9. Co-administration may lead to increased exposure to CYP2C9 substrates; however, the clinical impact of this has not yet been determined.
Empagliflozin: (Moderate) When empagliflozin is initiated in patients already receiving loop diuretics, volume depletion can occur. Patients with impaired renal function, low systolic blood pressure, or who are elderly may also be at a greater risk for volume depletion and perhaps symptomatic hypotension. Before initiating empagliflozin in patients with one or more of these characteristics, volume status should be assessed and corrected. Monitor for signs and symptoms after initiating therapy. Loop diuretics can decrease the hypoglycemic effects of antidiabetic agents by producing an increase in blood glucose concentrations. Patients receiving empagliflozin should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary.
Empagliflozin; Linagliptin: (Moderate) When empagliflozin is initiated in patients already receiving loop diuretics, volume depletion can occur. Patients with impaired renal function, low systolic blood pressure, or who are elderly may also be at a greater risk for volume depletion and perhaps symptomatic hypotension. Before initiating empagliflozin in patients with one or more of these characteristics, volume status should be assessed and corrected. Monitor for signs and symptoms after initiating therapy. Loop diuretics can decrease the hypoglycemic effects of antidiabetic agents by producing an increase in blood glucose concentrations. Patients receiving empagliflozin should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. (Minor) Loop diurectics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between these drugs and all antidiabetic agents, such as linagliptin. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if these drugs are initiated.
Empagliflozin; Linagliptin; Metformin: (Moderate) When empagliflozin is initiated in patients already receiving loop diuretics, volume depletion can occur. Patients with impaired renal function, low systolic blood pressure, or who are elderly may also be at a greater risk for volume depletion and perhaps symptomatic hypotension. Before initiating empagliflozin in patients with one or more of these characteristics, volume status should be assessed and corrected. Monitor for signs and symptoms after initiating therapy. Loop diuretics can decrease the hypoglycemic effects of antidiabetic agents by producing an increase in blood glucose concentrations. Patients receiving empagliflozin should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. (Minor) Hyperglycemia has been detected during torsemide therapy, but the incidence is low. Because of this, a potential pharmacodynamic interaction exists between torsemide and all antidiabetic agents, including metformin. Monitor blood glucose. (Minor) Loop diurectics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between these drugs and all antidiabetic agents, such as linagliptin. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if these drugs are initiated.
Empagliflozin; Metformin: (Moderate) When empagliflozin is initiated in patients already receiving loop diuretics, volume depletion can occur. Patients with impaired renal function, low systolic blood pressure, or who are elderly may also be at a greater risk for volume depletion and perhaps symptomatic hypotension. Before initiating empagliflozin in patients with one or more of these characteristics, volume status should be assessed and corrected. Monitor for signs and symptoms after initiating therapy. Loop diuretics can decrease the hypoglycemic effects of antidiabetic agents by producing an increase in blood glucose concentrations. Patients receiving empagliflozin should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. (Minor) Hyperglycemia has been detected during torsemide therapy, but the incidence is low. Because of this, a potential pharmacodynamic interaction exists between torsemide and all antidiabetic agents, including metformin. Monitor blood glucose.
Enalapril, Enalaprilat: (Major) Discontinue the loop diuretic prior to starting enalapril, if possible, or start enalapril at the lower dose of 2.5 mg/day. Monitor blood pressure and renal function during concomitant use, particularly when doses are increased. Concomitant use may increase the risk for hypotension or renal failure.
Enalapril; Hydrochlorothiazide, HCTZ: (Major) Discontinue the loop diuretic prior to starting enalapril, if possible, or start enalapril at the lower dose of 2.5 mg/day. Monitor blood pressure and renal function during concomitant use, particularly when doses are increased. Concomitant use may increase the risk for hypotension or renal failure. (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
Ephedrine: (Major) The cardiovascular effects of sympathomimetics, such as ephedrine, may reduce the antihypertensive effects produced by loop diuretics. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Ephedrine; Guaifenesin: (Major) The cardiovascular effects of sympathomimetics, such as ephedrine, may reduce the antihypertensive effects produced by loop diuretics. Blood pressure and heart rates should be monitored closely to confirm that the desired antihypertensive effect is achieved.
Epinephrine: (Moderate) Monitor blood pressure, heart rate, and serum potassium during concomitant epinephrine and loop diuretic use. Loop diuretics may antagonize the pressor effects and potentiate the arrhythmogenic and hypokalemic effects of epinephrine.
Epoprostenol: (Moderate) Epoprostenol can have additive effects when administered with other antihypertensive agents. These effects can be used to therapeutic advantage, but dosage adjustments may be necessary.
Eprosartan: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative.
Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative. (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
Ertugliflozin; Metformin: (Minor) Hyperglycemia has been detected during torsemide therapy, but the incidence is low. Because of this, a potential pharmacodynamic interaction exists between torsemide and all antidiabetic agents, including metformin. Monitor blood glucose.
Ertugliflozin; Sitagliptin: (Minor) 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. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if these drugs are initiated.
Escitalopram: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and escitalopram use; consider discontinuing escitalopram if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Esomeprazole: (Moderate) Monitor magnesium concentration before and periodically during concomitant esomeprazole and loop diuretic use due to risk for hypomagnesemia.
Estradiol: (Minor) Estrogens can induce fluid retention and may increase blood pressure in some patients; patients who are receiving antihypertensive agents concurrently with hormone therapy should be monitored for antihypertensive effectiveness.
Etodolac: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain.
Etomidate: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Exenatide: (Minor) Loop diuretics, such as bumetanide, furosemide, and torsemide, may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between these drugs and all antidiabetic agents, including incretin mimetics. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if these drugs are initiated.
Fenofibric Acid: (Minor) At therapeutic concentrations, fenofibric acid is a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C9 substrates, such as torsemide, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of torsemide during coadministration with fenofibric acid.
Fenoprofen: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain.
Fentanyl: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and fentanyl; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Fexofenadine; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Fish Oil, Omega-3 Fatty Acids (Dietary Supplements): (Moderate) Monitor blood pressure during concomitant fish oil and loop diuretic use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Fluconazole: (Moderate) Monitor the diuretic effect and blood pressure if torsemide and fluconazole are administered together. The torsemide dose may need to be reduced. Concomitant use of torsemide and fluconazole can decrease torsemide clearance and increase torsemide plasma concentrations. Torsemide is a substrate of CYP2C9; fluconazole inhibits CYP2C9.
Fludrocortisone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
Flunisolide: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
Fluoxetine: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and fluoxetine use; consider discontinuing fluoxetine if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Flurbiprofen: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain.
Fluticasone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
Fluticasone; Salmeterol: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
Fluticasone; Umeclidinium; Vilanterol: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
Fluticasone; Vilanterol: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
Fluvoxamine: (Moderate) Patients receiving a diuretic during treatment with fluvoxamine may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hyponatremia due to SIADH has been reported during therapy with SSRIs. Cases involving serum sodium levels lower than 110 mmol/L have occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of fluvoxamine should be considered in patients who develop symptomatic hyponatremia.
Formoterol; Mometasone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
Foscarnet: (Moderate) Avoid concurrent use of loop diuretics with foscarnet. Coadministration may impair the renal tubular secretion of foscarnet, thereby increasing the possibility for toxicity. When use of a diuretic is indicated in patients being treated with foscarnet, consider a thiazide diuretic.
Fosinopril: (Major) Discontinue the loop diuretic prior to starting fosinopril, if possible, or start fosinopril at a lower dose. Monitor blood pressure and renal function during concomitant use, particularly when doses are increased. Concomitant use may increase the risk for hypotension or renal failure.
Fosinopril; Hydrochlorothiazide, HCTZ: (Major) Discontinue the loop diuretic prior to starting fosinopril, if possible, or start fosinopril at a lower dose. Monitor blood pressure and renal function during concomitant use, particularly when doses are increased. Concomitant use may increase the risk for hypotension or renal failure. (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
General anesthetics: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Ginseng, Panax ginseng: (Major) Ginseng may decrease the effectiveness of loop diuretics. One case report described a temporal relationship between the use of ginseng and resistance to furosemide therapy, resulting in edema, hypertension, and hospitalization on 2 separate occasions. Other nutritional products were taken concurrently by the patient were not specified in the report. A mechanism of action or causal relationship has not been definitively established.
Glipizide; Metformin: (Minor) Hyperglycemia has been detected during torsemide therapy, but the incidence is low. Because of this, a potential pharmacodynamic interaction exists between torsemide and all antidiabetic agents, including metformin. Monitor blood glucose.
Glyburide; Metformin: (Minor) Hyperglycemia has been detected during torsemide therapy, but the incidence is low. Because of this, a potential pharmacodynamic interaction exists between torsemide and all antidiabetic agents, including metformin. Monitor blood glucose.
Granisetron: (Moderate) According to the manufacturer, caution is warranted when administering granisetron to patients with preexisting electrolyte abnormalities. Patients taking certain diuretics may develop an electrolyte abnormality that may lead to cardiac dysrhythmias and/or QT prolongation. Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs such as loop diuretics and thiazide diuretics, increasing the potential for cardiac arrhythmias.
Guaifenesin; Hydrocodone: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and hydrocodone; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Guaifenesin; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Guaifenesin; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Haloperidol: (Moderate) Caution is advisable during concurrent use of haloperidol and loop diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with haloperidol. Concomitant use may also cause additive hypotension.
Homatropine; Hydrocodone: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and hydrocodone; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Hydralazine; Isosorbide Dinitrate, ISDN: (Moderate) Monitor blood pressure during concomitant loop diuretic and nitrate use due to risk for additive hypotension; dosage adjustments may be necessary.
Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
Hydrochlorothiazide, HCTZ; Moexipril: (Major) Discontinue the loop diuretic prior to starting moexipril, if possible, or start moexipril at the lower dose of 3.75 mg/day. Monitor blood pressure and renal function during concomitant use, particularly when doses are increased. Concomitant use may increase the risk for hypotension or renal failure. (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
Hydrocodone: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and hydrocodone; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Hydrocodone; Ibuprofen: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and hydrocodone; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Hydrocodone; Pseudoephedrine: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and hydrocodone; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Hydrocortisone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
Hydromorphone: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when loop diuretics are administered with hydromorphone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Ibandronate: (Moderate) When the intravenous formulation of ibandronate is used for the treatment of hypercalcemia of malignancy, combination therapy with loop diuretics should be used with caution in order to avoid hypocalcemia. In patients with hypercalcemia of malignancy, the initial treatment typically includes the use of loop diuretics, in combination with saline hydration, however, diuretic therapy should not be employed prior to correction of hypovolemia and dehydration.
Ibuprofen lysine: (Moderate) Ibuprofen lysine may reduce the effect of diuretics; diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated patients. During coadministration of NSAIDs and diuretic therapy, patients should be monitored for changes in the effectiveness of their diuretic therapy and for signs and symptoms of renal impairment.
Ibuprofen: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain.
Ibuprofen; Famotidine: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain.
Ibuprofen; Oxycodone: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and oxycodone; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Ibuprofen; Pseudoephedrine: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Iloperidone: (Moderate) Secondary to alpha-blockade, iloperidone can produce vasodilation that may result in additive effects during concurrent use with antihypertensive agents. The potential reduction in blood pressure can precipitate orthostatic hypotension and associated dizziness, tachycardia, and syncope. If concurrent use of iloperidone and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known.
Iloprost: (Moderate) Further reductions in blood pressure may occur when inhaled iloprost is administered to patients receiving other antihypertensive agents.
Incretin Mimetics: (Minor) Loop diuretics, such as bumetanide, furosemide, and torsemide, may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between these drugs and all antidiabetic agents, including incretin mimetics. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if these drugs are initiated.
Indomethacin: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain.
Inotersen: (Moderate) Use caution with concomitant use of inotersen and diuretics due to the risk of glomerulonephritis and nephrotoxicity.
Insulin Degludec; Liraglutide: (Minor) Loop diuretics, such as bumetanide, furosemide, and torsemide, may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between these drugs and all antidiabetic agents, including incretin mimetics. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if these drugs are initiated.
Insulin Glargine; Lixisenatide: (Minor) Loop diuretics, such as bumetanide, furosemide, and torsemide, may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between these drugs and all antidiabetic agents, including incretin mimetics. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if these drugs are initiated.
Insulins: (Minor) Monitor patients receiving insulin closely for worsening glycemic control when bumetanide, furosemide, and torsemide are instituted. Bumetanide, furosemide, and torsemide may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between these drugs and all antidiabetic agents.
Intravenous Lipid Emulsions: (Moderate) Monitor blood pressure during concomitant fish oil and loop diuretic use. Concomitant use may result in additive hypotension; high doses of fish oil may produce a blood pressure lowering effect.
Irbesartan: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative.
Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative. (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
Isocarboxazid: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
Isoflurane: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Monitor the diuretic effect and blood pressure if torsemide and rifampin are administered together. The torsemide dose may need to be increased. Concomitant use of torsemide and rifampin can increase torsemide clearance and decrease torsemide plasma concentrations. Torsemide is a substrate of CYP2C9; rifampin induces CYP2C9.
Isoniazid, INH; Rifampin: (Moderate) Monitor the diuretic effect and blood pressure if torsemide and rifampin are administered together. The torsemide dose may need to be increased. Concomitant use of torsemide and rifampin can increase torsemide clearance and decrease torsemide plasma concentrations. Torsemide is a substrate of CYP2C9; rifampin induces CYP2C9.
Isoproterenol: (Moderate) The pharmacologic effects of isoproterenol may cause an increase in blood pressure. If isoproterenol is used concomitantly with antihypertensives, the blood pressure should be monitored as the administration of isoproterenol can compromise the effectiveness of antihypertensive agents.
Isosorbide Dinitrate, ISDN: (Moderate) Monitor blood pressure during concomitant loop diuretic and nitrate use due to risk for additive hypotension; dosage adjustments may be necessary.
Isosorbide Mononitrate: (Moderate) Monitor blood pressure during concomitant loop diuretic and nitrate use due to risk for additive hypotension; dosage adjustments may be necessary.
Ivacaftor: (Minor) Increased monitoring is recommended if ivacaftor is administered concurrently with CYP2C9 substrates, such as torsemide. In vitro studies showed ivacaftor to be a weak inhibitor of CYP2C9. Co-administration may lead to increased exposure to CYP2C9 substrates; however, the clinical impact of this has not yet been determined.
Ketamine: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Ketoprofen: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain.
Ketorolac: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain.
Lactulose: (Moderate) Loop diuretics may increase the risk of hypokalemia especially in patients receiving prolonged therapy with laxatives. Monitor serum potassium levels to determine the need for potassium supplementation and/or alteration in drug therapy.
Lansoprazole: (Moderate) Monitor magnesium concentration before and periodically during concomitant lansoprazole and loop diuretic use due to risk for hypomagnesemia.
Lansoprazole; Amoxicillin; Clarithromycin: (Moderate) Monitor magnesium concentration before and periodically during concomitant lansoprazole and loop diuretic use due to risk for hypomagnesemia.
Levodopa: (Moderate) Monitor blood pressure during concomitant levodopa and loop diuretic use due to risk for additive hypotension; a loop diuretic dosage adjustment may be necessary. Symptomatic postural hypotension has occurred when carbidopa; levodopa was added in a person receiving antihypertensive drugs.
Levomilnacipran: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and serotonin norepinephrine reuptake inhibitor (SNRI) use; consider discontinuing the SNRI if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Levorphanol: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when loop diuretics are administered with levorphanol. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Lidocaine; Epinephrine: (Moderate) Monitor blood pressure, heart rate, and serum potassium during concomitant epinephrine and loop diuretic use. Loop diuretics may antagonize the pressor effects and potentiate the arrhythmogenic and hypokalemic effects of epinephrine.
Linagliptin: (Minor) Loop diurectics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between these drugs and all antidiabetic agents, such as linagliptin. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if these drugs are initiated.
Linagliptin; Metformin: (Minor) Hyperglycemia has been detected during torsemide therapy, but the incidence is low. Because of this, a potential pharmacodynamic interaction exists between torsemide and all antidiabetic agents, including metformin. Monitor blood glucose. (Minor) Loop diurectics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between these drugs and all antidiabetic agents, such as linagliptin. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if these drugs are initiated.
Liraglutide: (Minor) Loop diuretics, such as bumetanide, furosemide, and torsemide, may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between these drugs and all antidiabetic agents, including incretin mimetics. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if these drugs are initiated.
Lisdexamfetamine: (Minor) Lisdexamfetamine may increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as loop diuretics. Close monitoring of blood pressure is advised.
Lisinopril: (Major) Discontinue the loop diuretic prior to starting lisinopril, if possible, or start lisinopril at the lower dose of 5 mg/day. Monitor blood pressure and renal function during concomitant use, particularly when doses are increased. Concomitant use may increase the risk for hypotension or renal failure.
Lisinopril; Hydrochlorothiazide, HCTZ: (Major) Discontinue the loop diuretic prior to starting lisinopril, if possible, or start lisinopril at the lower dose of 5 mg/day. Monitor blood pressure and renal function during concomitant use, particularly when doses are increased. Concomitant use may increase the risk for hypotension or renal failure. (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
Lithium: (Moderate) Monitor serum electrolyte and lithium concentrations during concomitant loop diuretic use; reduce the lithium dose based on serum lithium concentration and clinical response. Diuretic-induced sodium loss may reduce lithium clearance and increase lithium serum concentrations.
Lixisenatide: (Minor) Loop diuretics, such as bumetanide, furosemide, and torsemide, may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between these drugs and all antidiabetic agents, including incretin mimetics. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if these drugs are initiated.
Loratadine; Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Losartan: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative.
Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may res ult in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative. (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
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.
Lumacaftor; Ivacaftor: (Minor) Although the clinical significance of this interaction is unknown, concurrent use of torsemide and lumacaftor; ivacaftor may alter torsemide exposure; caution and monitoring are advised if these drugs are used together. Torsemide is a substrate of CYP2C9. In vitro data suggest that lumacaftor; ivacaftor may induce and/or inhibit CYP2C9. The net effect of lumacaftor; ivacaftor on CYP2C9-mediated metabolism is not clear, but CYP2C9 substrate exposure may be affected leading to decreased efficacy or increased or prolonged therapeutic effects and adverse events.
Lumacaftor; Ivacaftor: (Minor) Increased monitoring is recommended if ivacaftor is administered concurrently with CYP2C9 substrates, such as torsemide. In vitro studies showed ivacaftor to be a weak inhibitor of CYP2C9. Co-administration may lead to increased exposure to CYP2C9 substrates; however, the clinical impact of this has not yet been determined.
Lurasidone: (Moderate) Due to the antagonism of lurasidone at alpha-1 adrenergic receptors, the drug may enhance the hypotensive effects of alpha-blockers and other antihypertensive agents. If concurrent use of lurasidone and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known.
Magnesium Citrate: (Moderate) Monitor potassium concentration before and during concomitant laxative, such as magnesium citrate, and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary.
Magnesium Hydroxide: (Moderate) Monitor potassium concentration before and during concomitant laxative, such as magnesium hydroxide, and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary.
Magnesium Sulfate; Potassium Sulfate; Sodium Sulfate: (Moderate) Use caution when prescribing sulfate salt bowel preparation in patients taking concomitant medications that may affect renal function such as diuretics.
Mannitol: (Major) Avoid use of other diuretics with mannitol, if possible. Concomitant administration may potentiate the renal toxicity of mannitol.
Meclofenamate Sodium: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain.
Mefenamic Acid: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain.
Meglitinides: (Minor) Loop diuretics have been associated with hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between loop diuretics and all antidiabetic agents. Monitor for a loss of diabetic control.
Meloxicam: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain.
Meperidine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when loop diuretics are administered with meperidine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Metformin: (Minor) Hyperglycemia has been detected during torsemide therapy, but the incidence is low. Because of this, a potential pharmacodynamic interaction exists between torsemide and all antidiabetic agents, including metformin. Monitor blood glucose.
Metformin; Repaglinide: (Minor) Hyperglycemia has been detected during torsemide therapy, but the incidence is low. Because of this, a potential pharmacodynamic interaction exists between torsemide and all antidiabetic agents, including metformin. Monitor blood glucose. (Minor) Loop diuretics have been associated with hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between loop diuretics and all antidiabetic agents. Monitor for a loss of diabetic control.
Metformin; Rosiglitazone: (Minor) Hyperglycemia has been detected during torsemide therapy, but the incidence is low. Because of this, a potential pharmacodynamic interaction exists between torsemide and all antidiabetic agents, including metformin. Monitor blood glucose. (Minor) Hyperglycemia has been detected during torsemide therapy, but the incidence is low. Patients on antidiabetic medications should monitor their blood glucose regularly if torsemide is prescribed.
Metformin; Saxagliptin: (Minor) Hyperglycemia has been detected during torsemide therapy, but the incidence is low. Because of this, a potential pharmacodynamic interaction exists between torsemide and all antidiabetic agents, including metformin. Monitor blood glucose. (Minor) 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. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if these drugs are initiated.
Metformin; Sitagliptin: (Minor) Hyperglycemia has been detected during torsemide therapy, but the incidence is low. Because of this, a potential pharmacodynamic interaction exists between torsemide and all antidiabetic agents, including metformin. Monitor blood glucose. (Minor) 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. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if these drugs are initiated.
Methadone: (Moderate) Diuretics can cause electrolyte disturbances such as hypomagnesemia and hypokalemia, which may prolong the QT interval. As methadone may also prolong the QT interval, cautious coadministration with diuretics is needed.
Methamphetamine: (Minor) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as loop diuretics. Close monitoring of blood pressure is advised.
Methazolamide: (Moderate) Loop diuretics may increase the risk of hypokalemia if used concurrently with methazolamide. Monitor serum potassium levels to determine the need for potassium supplementation and/or alteration in drug therapy. There may also be an additive diuretic or hyperuricemic effect.
Methohexital: (Moderate) Concurrent use of methohexital and antihypertensive agents increases the risk of developing hypotension.
Methyclothiazide: (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
Methylcellulose: (Moderate) Loop diuretics may increase the risk of hypokalemia especially in patients receiving prolonged therapy with laxatives. Monitor serum potassium levels to determine the need for potassium supplementation and/or alteration in drug therapy.
Methylphenidate Derivatives: (Moderate) Monitor blood pressure during concomitant loop diuretic and methylphenidate use; a loop diuretic dose adjustment may be necessary. Methylphenidate may decrease the effectiveness of medications used to treat hypertension.
Methylprednisolone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
Metolazone: (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
Miconazole: (Minor) No formal drug interaction studies have been performed with buccal miconazole. Systemic absorption of miconazole following buccal administration is minimal. Vaginal and topical preparations are not likely to interact. However, the diuretic effect and blood pressure response may be affected if torsemide is administered with a CYP2C9 inhibitor. Torsemide is a substrate of CYP2C9; miconazole inhibits CYP2C9. Concomitant use of torsemide and miconazole can theoretically decrease torsemide clearance and increase torsemide plasma concentrations.
Miglitol: (Minor) Loop diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely.
Milnacipran: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and serotonin norepinephrine reuptake inhibitor (SNRI) use; consider discontinuing the SNRI if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Milrinone: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
Mineral Oil: (Moderate) Loop diuretics may increase the risk of hypokalemia especially in patients receiving prolonged therapy with laxatives. Monitor serum potassium levels to determine the need for potassium supplementation and/or alteration in drug therapy.
Mirtazapine: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and mirtazapine use; consider discontinuing mirtazapine if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Mivacurium: (Moderate) Concomitant use of neuromuscular blockers and loop diuretics may prolong neuromuscular blockade, possibly due to hypokalemia or alterations in potassium concentrations across the end-plate membrane.
Moexipril: (Major) Discontinue the loop diuretic prior to starting moexipril, if possible, or start moexipril at the lower dose of 3.75 mg/day. Monitor blood pressure and renal function during concomitant use, particularly when doses are increased. Concomitant use may increase the risk for hypotension or renal failure.
Mometasone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
Morphine: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and morphine; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Morphine; Naltrexone: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and morphine; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Nabumetone: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain.
Naproxen: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain.
Naproxen; Esomeprazole: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. (Moderate) Monitor magnesium concentration before and periodically during concomitant esomeprazole and loop diuretic use due to risk for hypomagnesemia.
Naproxen; Pseudoephedrine: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain. (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Nateglinide: (Minor) Loop diuretics have been associated with hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between loop diuretics and all antidiabetic agents. Monitor for a loss of diabetic control.
Nebivolol; Valsartan: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative.
Nefazodone: (Minor) Although relatively infrequent, nefazodone may cause orthostatic hypotension in some patients; this effect may be additive with antihypertensive agents. Blood pressure monitoring and dosage adjustments of either drug may be necessary.
Neomycin; Polymyxin B; Bacitracin: (Minor) Additive nephrotoxicity may occur with concurrent use of systemic bacitracin and other nephrotoxic agents. When possible, avoid concomitant administration of systemic bacitracin and other nephrotoxic drugs such as loop diuretics. Topical administration of any preparation containing bacitracin, especially when applied to large surface areas, also should not be given with other drugs that have a nephrotoxic potential.
Nesiritide, BNP: (Major) The potential for hypotension may be increased when coadministering nesiritide with antihypertensive agents.
Neuromuscular blockers: (Moderate) Concomitant use of neuromuscular blockers and loop diuretics may prolong neuromuscular blockade, possibly due to hypokalemia or alterations in potassium concentrations across the end-plate membrane.
Niacin, Niacinamide: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
Niacin; Simvastatin: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
Nitrates: (Moderate) Monitor blood pressure during concomitant loop diuretic and nitrate use due to risk for additive hypotension; dosage adjustments may be necessary.
Nitroglycerin: (Moderate) Monitor blood pressure during concomitant loop diuretic and nitrate use due to risk for additive hypotension; dosage adjustments may be necessary.
Nitroprusside: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
Non-Ionic Contrast Media: (Major) Do not use diuretics before non-ionic contrast media administration. Concomitant use of diuretics and non-ionic contrast media may increase the risk for acute kidney injury, including renal failure.
Norepinephrine: (Moderate) Diuretics can cause decreased arterial responsiveness to norepinephrine, but the effect is not sufficient to preclude their coadministration.
Octreotide: (Moderate) Patients receiving diuretics or other agents to control fluid and electrolyte balance may require dosage adjustments while receiving octreotide due to additive effects.
Olanzapine: (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents.
Olanzapine; Fluoxetine: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and fluoxetine use; consider discontinuing fluoxetine if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia. (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents.
Olanzapine; Samidorphan: (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents.
Oliceridine: (Moderate) Monitor patients for signs of diminished diuresis and/or effects on blood pressure if diuretics are used concomitantly with oliceridine; increase the dosage of the diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Olmesartan: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative. (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative. (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
Olopatadine; Mometasone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
Omeprazole: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and loop diuretic use due to risk for hypomagnesemia.
Omeprazole; Amoxicillin; Rifabutin: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and loop diuretic use due to risk for hypomagnesemia.
Omeprazole; Sodium Bicarbonate: (Moderate) Monitor magnesium concentration before and periodically during concomitant omeprazole and loop diuretic use due to risk for hypomagnesemia.
Oritavancin: (Moderate) Torsemide is metabolized by CYP2C9; oritavancin is a weak CYP2C9 inhibitor. Coadministration may result in elevated torsemide plasma concentrations. If these drugs are administered concurrently, monitor patients for signs of torsemide toxicity, such as dehydration, hypokalemia, or hypomagnesemia.
Oxandrolone: (Moderate) Monitor the diuretic effect and blood pressure if torsemide and oxandrolone are administered together. The torsemide dose may need to be reduced. Concomitant use of torsemide and oxandrolone can decrease torsemide clearance and increase torsemide plasma concentrations. Torsemide is a substrate of CYP2C9; oxandrolone inhibits CYP2C9.
Oxaprozin: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain.
Oxybutynin: (Minor) Diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Oxycodone: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and oxycodone; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Oxymetazoline: (Major) The vasoconstricting actions of oxymetazoline, an alpha adrenergic agonist, may reduce the antihypertensive effects produced by diuretics. If these drugs are used together, closely monitor for changes in blood pressure.
Oxymorphone: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when loop diuretics are administered with oxymorphone. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Paliperidone: (Moderate) Paliperidone may cause orthostatic hypotension, thereby enhancing the hypotensive effects of antihypertensive agents. Orthostatic vital signs should be monitored in patients receiving paliperidone and loop diuretics who are susceptible to hypotension.
Pamidronate: (Moderate) Because both loop diuretics and intravenously administered bisphosphonates (i.e., alendronate, ibandronate, pamidronate, and zoledronic acid) can cause a decrease in serum calcium, caution is advised when used concomitantly in the treatment of hypercalcemia of malignancy in order to avoid hypocalcemia. In patients with hypercalcemia of malignancy, the initial treatment typically includes the use of loop diuretics, in combination with saline hydration, however, diuretic therapy should not be employed prior to correction of hypovolemia and dehydration.
Pancuronium: (Moderate) Concomitant use of neuromuscular blockers and loop diuretics may prolong neuromuscular blockade, possibly due to hypokalemia or alterations in potassium concentrations across the end-plate membrane.
Pantoprazole: (Moderate) Monitor magnesium concentration before and periodically during concomitant pantoprazole and loop diuretic use due to risk for hypomagnesemia.
Paroxetine: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and paroxetine use; consider discontinuing paroxetine if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Pasireotide: (Moderate) Cautious use of pasireotide and loop diuretics is advised as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pasireotide. Assess the patient's potassium and magnesium concentration before and periodically during pasireotide receipt. Correct hypokalemia and hypomagnesemia before pasireotide receipt.
Pentamidine: (Moderate) Drugs that are associated with hypokalemia and/or hypomagnesemia such as loop diuretics should be used with caution in patients also receiving pentamidine. Since pentamidine may cause QT prolongation independently of electrolyte imbalances, the risk for cardiac arrhythmias is potentiated by the concomitant use of agents associated with electrolyte loss. .
Pentazocine: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when loop diuretics are administered with pentazocine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Pentazocine; Naloxone: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when loop diuretics are administered with pentazocine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Pentoxifylline: (Moderate) Pentoxifylline has been used concurrently with antihypertensive drugs (beta blockers, diuretics) without observed problems. Small decreases in blood pressure have been observed in some patients treated with pentoxifylline; periodic systemic blood pressure monitoring is recommended for patients receiving concomitant antihypertensives. If indicated, dosage of the antihypertensive agents should be reduced.
Perindopril: (Major) Discontinue the loop diuretic prior to starting perindopril, if possible, or start perindopril at a lower dose. Monitor blood pressure and renal function during concomitant use, particularly when doses are increased. Concomitant use may increase the risk for hypotension or renal failure.
Perindopril; Amlodipine: (Major) Discontinue the loop diuretic prior to starting perindopril, if possible, or start perindopril at a lower dose. Monitor blood pressure and renal function during concomitant use, particularly when doses are increased. Concomitant use may increase the risk for hypotension or renal failure.
Phenelzine: (Moderate) Monitor blood pressure during concomitant loop diuretic and phenelzine use due to risk for additive hypotension.
Phentermine; Topiramate: (Moderate) Monitor potassium concentration before and during concomitant topiramate and loop diuretic use due to risk for additive hypokalemia. Topiramate can increase the risk of hypokalemia through its inhibition of carbonic anhydrase activity and concomitant use with loop diuretics may further potentiate potassium-wasting.
Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Phenytoin: (Moderate) The concomitant use of phenytoin, a substrate of CYP2C9 with a narrow therapeutic range, and torsemide, a CYP2C9 inhibitor, may result in increased plasma concentrations of phenytoin. If these drugs are coadministered, monitor patients for signs of phenytoin toxicity. Monitoring phenytoin concentrations may be necessary.
Pimozide: (Moderate) Caution is advisable during concurrent use of pimozide and loop diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with pimozide. Potassium deficiencies should be corrected prior to treatment with pimozide and normalized potassium levels should be maintained during treatment.
Pioglitazone: (Minor) Hyperglycemia has been detected during torsemide therapy, but the incidence is low. Patients on antidiabetic medications should monitor their blood glucose regularly if torsemide is prescribed.
Pioglitazone; Glimepiride: (Minor) Hyperglycemia has been detected during torsemide therapy, but the incidence is low. Patients on antidiabetic medications should monitor their blood glucose regularly if torsemide is prescribed.
Pioglitazone; Metformin: (Minor) Hyperglycemia has been detected during torsemide therapy, but the incidence is low. Because of this, a potential pharmacodynamic interaction exists between torsemide and all antidiabetic agents, including metformin. Monitor blood glucose. (Minor) Hyperglycemia has been detected during torsemide therapy, but the incidence is low. Patients on antidiabetic medications should monitor their blood glucose regularly if torsemide is prescribed.
Piroxicam: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain.
Polycarbophil: (Moderate) Loop diuretics may increase the risk of hypokalemia, especially in patients receiving prolonged therapy with laxatives such as calcium polycarbophil. Monitor serum potassium to determine the need for potassium supplementation and/or alteration in drug therapy.
Polyethylene Glycol: (Moderate) Monitor renal function and serum electrolytes and ensure adequate hydration before and after concomitant loop diuretic and polyethylene glycol 3350 use. Concomitant use may increase the risk for fluid and electrolyte abnormalities and renal injury.
Polyethylene Glycol; Electrolytes: (Moderate) Monitor renal function and serum electrolytes and ensure adequate hydration before and after concomitant loop diuretic and polyethylene glycol 3350 use. Concomitant use may increase the risk for fluid and electrolyte abnormalities and renal injury. (Moderate) Use caution when prescribing sulfate salt bowel preparation in patients taking concomitant medications that may affect renal function such as diuretics.
Polyethylene Glycol; Electrolytes; Ascorbic Acid: (Moderate) Monitor renal function and serum electrolytes and ensure adequate hydration before and after concomitant loop diuretic and polyethylene glycol 3350 use. Concomitant use may increase the risk for fluid and electrolyte abnormalities and renal injury. (Moderate) Use caution when prescribing sulfate salt bowel preparation in patients taking concomitant medications that may affect renal function such as diuretics.
Polyethylene Glycol; Electrolytes; Bisacodyl: (Moderate) Loop diuretics may increase the risk of hypokalemia especially in patients receiving prolonged therapy with laxatives. Monitor serum potassium levels to determine the need for potassium supplementation and/or alteration in drug therapy. (Moderate) Monitor renal function and serum electrolytes and ensure adequate hydration before and after concomitant loop diuretic and polyethylene glycol 3350 use. Concomitant use may increase the risk for fluid and electrolyte abnormalities and renal injury.
Polymyxin B: (Moderate) Systemic polymyxin B is nephrotoxic and should be used cautiously with loop diuretics, which may cause azotemia and may increase the risk for renal toxicity when coadministered. Close monitoring of renal status and for drug toxicity is recommended. Diminishing urine output and a rising BUN are indications to discontinue systemic polymyxin B therapy.
Pramlintide: (Minor) Loop diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between these drugs and all antidiabetic agents. Monitor patient for diabetic control.
Prazosin: (Moderate) The first dose response (acute postural hypotension) of prazosin may be exaggerated in patients who are receiving loop diuretics. This effect can be minimized by reducing the prazosin dose to 1 to 2 mg three times a day, by introducing the loop diuretic cautiously, and then by retitrating prazosin to clinical response.
Prednisolone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
Prednisone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
Prilocaine; Epinephrine: (Moderate) Monitor blood pressure, heart rate, and serum potassium during concomitant epinephrine and loop diuretic use. Loop diuretics may antagonize the pressor effects and potentiate the arrhythmogenic and hypokalemic effects of epinephrine.
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.
Promethazine; Phenylephrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving decongestant sympathomimetics at recommended doses do not appear at high risk for significant elevations in blood pressure, however, increased blood pressure has been reported in some patients.
Propofol: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
Pseudoephedrine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Pseudoephedrine; Triprolidine: (Moderate) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by diuretics. Well-controlled hypertensive patients receiving pseudoephedrine at recommended doses do not appear at high risk for significant elevations in blood pressure; however, increased blood pressure (especially systolic hypertension) has been reported in some patients.
Psyllium: (Moderate) Loop diuretics may increase the risk of hypokalemia especially in patients receiving prolonged therapy with laxatives. Monitor serum potassium levels to determine the need for potassium supplementation and/or alteration in drug therapy.
Quinapril: (Major) Discontinue the loop diuretic prior to starting quinapril, if possible, or start quinapril at the lower dose of 5 mg/day. Monitor blood pressure and renal function during concomitant use, particularly when doses are increased. Concomitant use may increase the risk for hypotension or renal failure.
Quinapril; Hydrochlorothiazide, HCTZ: (Major) Discontinue the loop diuretic prior to starting quinapril, if possible, or start quinapril at the lower dose of 5 mg/day. Monitor blood pressure and renal function during concomitant use, particularly when doses are increased. Concomitant use may increase the risk for hypotension or renal failure. (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
Quinidine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
Rabeprazole: (Moderate) Proton pump inhibitors have been associated with hypomagnesemia. Hypomagnesemia occurs with loop diuretics (furosemide, bumetanide, torsemide, and ethacrynic acid). Low serum magnesium may lead to serious adverse events such as muscle spasm, seizures, and arrhythmias. Therefore, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and diuretics concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
Ramipril: (Major) Discontinue the loop diuretic prior to starting ramipril, if possible, or start ramipril at a lower dose. Monitor blood pressure and renal function during concomitant use, particularly when doses are increased. Concomitant use may increase the risk for hypotension or renal failure.
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.
Rifampin: (Moderate) Monitor the diuretic effect and blood pressure if torsemide and rifampin are administered together. The torsemide dose may need to be increased. Concomitant use of torsemide and rifampin can increase torsemide clearance and decrease torsemide plasma concentrations. Torsemide is a substrate of CYP2C9; rifampin induces CYP2C9.
Risperidone: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
Rocuronium: (Moderate) Concomitant use of neuromuscular blockers and loop diuretics may prolong neuromuscular blockade, possibly due to hypokalemia or alterations in potassium concentrations across the end-plate membrane.
Rosiglitazone: (Minor) Hyperglycemia has been detected during torsemide therapy, but the incidence is low. Patients on antidiabetic medications should monitor their blood glucose regularly if torsemide is prescribed.
Sacubitril; Valsartan: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative.
Salicylates: (Moderate) Salicylates may decrease the diuretic, natriuretic, and antihypertensive actions of diuretics, possibly through inhibition of renal prostaglandin synthesis. Patients receiving loop diuretics and salicylates should be monitored for changes in the effectiveness of their diuretic therapy.
Saxagliptin: (Minor) 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. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if these drugs are initiated.
Semaglutide: (Minor) Loop diuretics, such as bumetanide, furosemide, and torsemide, may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between these drugs and all antidiabetic agents, including incretin mimetics. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if these drugs are initiated.
Senna: (Minor) The risk of hypokalemia due to loop diuretics may be increased in patients receiving prolonged therapy with certain laxatives. Monitor serum potassium levels to determine the need for potassium supplementation and/or alteration in drug therapy in patients receiving loop diuretics. Senna rarely causes hypokalemia with proper use.
Serotonin norepinephrine reuptake inhibitors: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and serotonin norepinephrine reuptake inhibitor (SNRI) use; consider discontinuing the SNRI if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Sertraline: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and sertraline use; consider discontinuing sertraline if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Sevoflurane: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
Silodosin: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
Sitagliptin: (Minor) 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. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if these drugs are initiated.
Sodium Phosphate Monobasic Monohydrate; Sodium Phosphate Dibasic Anhydrous: (Moderate) Concomitant use of medicines with potential to alter renal perfusion or function such as diuretics, may increase the risk of acute phosphate nephropathy in patients receiving sodium phosphate monobasic monohydrate; sodium phosphate dibasic anhydrous. In addition, loop diuretics may increase the risk of hypokalemia especially in patients receiving prolonged therapy with laxatives. Monitor serum potassium levels to determine the need for potassium supplementation and/or alteration in drug therapy.
Sodium picosulfate; Magnesium oxide; Anhydrous citric acid: (Moderate) Use caution when prescribing sodium picosulfate; magnesium oxide; anhydrous citric acid in patients taking concomitant medications that may affect renal function such as diuretics. In addition, use caution in patients receiving drugs where hypokalemia is a particular risk.
Sodium Polystyrene Sulfonate: (Moderate) Sodium polystyrene sulfonate should be used cautiously with other agents that can induce hypokalemia such as loop diuretics, insulins, or intravenous sodium bicarbonate. Because of differences in onset of action, sodium polystyrene sulfonate is often used with these agents. With appropriate monitoring, hypokalemia can be avoided.
Solifenacin: (Minor) Diuretics can increase urinary frequency, which may aggravate bladder symptoms. Risk versus benefit should be addressed in patients receiving diuretics and solifenacin.
Sorbitol: (Moderate) Loop diuretics may increase the risk of hypokalemia especially in patients receiving prolonged therapy with laxatives. Monitor serum potassium levels to determine the need for potassium supplementation and/or alteration in drug therapy.
Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
Streptozocin: (Minor) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents (e.g., aminoglycosides, amphotericin B, cisplatin, foscarnet, or diuretics) could exacerbate the renal insult.
Succinylcholine: (Moderate) Concomitant use of neuromuscular blockers and loop diuretics may prolong neuromuscular blockade, possibly due to hypokalemia or alterations in potassium concentrations across the end-plate membrane.
Sufentanil: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when loop diuretics are administered with sufentanil. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Sulfonylureas: (Minor) Hyperglycemia has been detected during torsemide therapy, but the incidence is low. Because of this, a potential pharmacodynamic interaction exists between torsemide and all antidiabetic agents. Monitor blood glucose.
Sulindac: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain.
Sumatriptan; Naproxen: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain.
Tapentadol: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when loop diuretics are administered with tapentadol. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone.
Telavancin: (Moderate) Concurrent or sequential use of telavancin with other potentially nephrotoxic drugs such as loop diuretics may lead to additive nephrotoxicity. Closely monitor renal function and adjust telavancin doses based on calculated creatinine clearance.
Telmisartan: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative.
Telmisartan; Amlodipine: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative.
Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative. (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
Tetracaine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Use extreme caution with the concomitant use of tetracaine and antihypertensive agents.
Tezacaftor; Ivacaftor: (Minor) Increased monitoring is recommended if ivacaftor is administered concurrently with CYP2C9 substrates, such as torsemide. In vitro studies showed ivacaftor to be a weak inhibitor of CYP2C9. Co-administration may lead to increased exposure to CYP2C9 substrates; however, the clinical impact of this has not yet been determined.
Thiazide diuretics: (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
Thiazolidinediones: (Minor) Hyperglycemia has been detected during torsemide therapy, but the incidence is low. Patients on antidiabetic medications should monitor their blood glucose regularly if torsemide is prescribed.
Thiothixene: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Tirzepatide: (Minor) Loop diuretics, such as bumetanide, furosemide, and torsemide, may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between these drugs and all antidiabetic agents, including incretin mimetics. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if these drugs are initiated.
Tizanidine: (Moderate) Monitor blood pressure during concomitant loop diuretic and tizanidine use due to risk for additive hypotension.
Tolmetin: (Moderate) If a nonsteroidal anti-inflammatory drug (NSAID) and a diuretic are used concurrently, carefully monitor the patient for signs and symptoms of decreased renal function and diuretic efficacy. Patients taking diuretics and NSAIDs concurrently are at higher risk of developing renal insufficiency. NSAIDs may reduce the natriuretic effect of diuretics in some patients. NSAIDs have been associated with an inhibition of prostaglandin synthesis, which may result in reduced renal blood flow leading to renal insufficiency and increases in blood pressure that are often accompanied by peripheral edema and weight gain.
Tolterodine: (Minor) Diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Tolvaptan: (Moderate) Monitor serum sodium closely if torsemide and tolvaptan are used together. Coadministration increases the risk of too rapid correction of serum sodium.
Topiramate: (Moderate) Monitor potassium concentration before and during concomitant topiramate and loop diuretic use due to risk for additive hypokalemia. Topiramate can increase the risk of hypokalemia through its inhibition of carbonic anhydrase activity and concomitant use with loop diuretics may further potentiate potassium-wasting.
Toremifene: (Moderate) Monitor for an increase in torsemide-related adverse reactions including diuretic effect and blood pressure if coadministration with toremifene is necessary; adjust the dose of torsemide if necessary. Torsemide is a CYP2C9 substrate and toremifene is a weak CYP2C9 inhibitor.
Tramadol: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and tramadol; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Tramadol; Acetaminophen: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and tramadol; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Trandolapril: (Major) Discontinue the loop diuretic prior to starting trandolapril, if possible, or start trandolapril at the lower dose of 0.5 mg/day. Monitor blood pressure and renal function during concomitant use, particularly when doses are increased. Concomitant use may increase the risk for hypotension or renal failure.
Trandolapril; Verapamil: (Major) Discontinue the loop diuretic prior to starting trandolapril, if possible, or start trandolapril at the lower dose of 0.5 mg/day. Monitor blood pressure and renal function during concomitant use, particularly when doses are increased. Concomitant use may increase the risk for hypotension or renal failure.
Tranylcypromine: (Contraindicated) The use of hypotensive agents and tranylcypromine is contraindicated by the manufacturer of tranylcypromine because the effects of hypotensive agents may be markedly potentiated.
Trazodone: (Minor) Due to additive hypotensive effects, patients receiving antihypertensive agents concurrently with trazodone may have excessive hypotension. Decreased dosage of the antihypertensive agent may be required when given with trazodone.
Triamcinolone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss.
Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
Trospium: (Minor) Diuretics can increase urinary frequency, which may aggravate bladder symptoms.
Valsartan: (Moderate) Coadministration of furosemide and Angiotensin-converting enzy me inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative.
Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Coadministration of furosemide and Angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor antagonists may result in severe hypotension and deterioration in renal function, including renal failure. Hyponatremia or hypovolemia predisposes patients to acute hypotensive episodes following initiation of ACE inhibitor therapy. While ACE inhibitors and loop diuretics are routinely administered together in the treatment of heart failure, if an ACE inhibitor is to be administered to a patient receiving furosemide, initial doses should be conservative. (Moderate) Monitor blood pressure, renal function, and serum electrolytes during concomitant loop diuretic and thiazide diuretic use; dosage adjustments may be necessary. Concomitant use may result in additive hypotension and fluid and/or electrolyte loss.
Vecuronium: (Moderate) Concomitant use of neuromuscular blockers and loop diuretics may prolong neuromuscular blockade, possibly due to hypokalemia or alterations in potassium concentrations across the end-plate membrane.
Vemurafenib: (Moderate) Concomitant use of vemurafenib and torsemide may result in increased torsemide concentrations. Vemurafenib is a CYP2C9 inhibitor and torsemide is a CYP2C9 substrate. Patients should be monitored for toxicity.
Venlafaxine: (Moderate) Monitor for signs and symptoms of hyponatremia during concomitant diuretic and serotonin norepinephrine reuptake inhibitor (SNRI) use; consider discontinuing the SNRI if symptomatic hyponatremia occurs and institute appropriate medical intervention. Concomitant use increases the risk for developing hyponatremia.
Vilazodone: (Moderate) Patients receiving vilazodone with medications known to cause hyponatremia, such as diuretics, may be at increased risk of developing hyponatremia. Hyponatremia has occurred in association with the use of antidepressants such as selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), and mirtazapine. Hyponatremia may manifest as headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness which may result in falls. Severe manifestations include hallucinations, syncope, seizure, coma, respiratory arrest, and death. Symptomatic hyponatremia may require discontinuation of vilazodone, as well as implementation of the appropriate medical interventions.
Vorinostat: (Moderate) Use vorinostat and loop diuretics together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Loop diuretics may cause electrolyte imbalances including low potassium; hypomagnesemia, hypokalemia, or hypocalcemia may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Vortioxetine: (Moderate) Patients receiving a diuretic during treatment with vortioxetine may be at greater risk of developing syndrome of inappropriate antidiuretic hormone secretion (SIADH). Clinically significant hyponatremia has been reported during therapy with vortioxetine. One case involving serum sodium levels lower than 110 mmol/l has occurred. Hyponatremia may be potentiated by agents which can cause sodium depletion such as diuretics. Discontinuation of vortioxetine should be considered in patients who develop symptomatic hyponatremia.
Warfarin: (Moderate) Use caution and frequently monitor the PT/INR of patients receiving concomitant therapy with warfarin and torsemide; adjust the dose of warfarin as appropriate. S-warfarin is a CYP2C9 substrate; torsemide is a CYP2C9 inhibitor. Coadministration may result in increases in PT/INR response.
Ziconotide: (Moderate) Patients taking diuretics with ziconotide may be at higher risk of depressed levels of consciousness. If altered consciousness occurs, consideration of diuretic cessation is warranted in addition to ziconotide discontinuation.
Ziprasidone: (Moderate) Monitor potassium and magnesium levels when loop diuretics are used during ziprasidone therapy. The risk of QT prolongation from ziprasidone is increased in the presence of hypokalemia or hypomagnesemia.
Zoledronic Acid: (Moderate) Loop diuretics should be used with caution in combination with zoledronic acid in order to avoid hypocalcemia. In patients with hypercalcemia of malignancy, the initial treatment typically includes the use of loop diuretics, in combination with saline hydration, however, diuretic therapy should not be employed prior to correction of hypovolemia and dehydration.

How Supplied

Demadex/SOAANZ/Torsemide Oral Tab: 5mg, 10mg, 20mg, 40mg, 60mg, 100mg

Maximum Dosage
Adults

10 mg/day PO for hypertension. Single doses greater than 40 mg PO have not been adequately studied for edema associated with hepatic cirrhosis; single doses greater than 200 mg PO have not been adequately studied for edema associated with heart failure or chronic renal failure.

Geriatric

10 mg/day PO for hypertension. Single doses greater than 40 mg PO have not been adequately studied for edema associated with hepatic cirrhosis; single doses greater than 200 mg PO have not been adequately studied for edema associated with heart failure or chronic renal failure.

Adolescents

Safety and efficacy have not been established.

Children

Safety and efficacy have not been established.

Infants

Safety and efficacy have not been established.

Neonates

Safety and efficacy have not been established.

Mechanism Of Action

Mechanism of Action: The actions of loop diuretics can be mediated by several mechanisms operating within the thick, medullary segment of the ascending loop of Henle. These include (a) interference with Na+/K+/2Cl- cotransport at the luminal surface, (b) Na-K pump, and (c) anion exchange. Similar to bumetanide, torsemide selectively blocks active sodium and chloride reabsorption in the thick ascending loop of Henle (mechanism (a) above) promoting rapid excretion of water, sodium and chloride. This action is a result of binding of the diuretic to a chloride ion binding site of the transport molecule. Torsemide also interferes with chloride channels, however, this appears to be a minor mechanism. Effects on potassium, calcium, or bicarbonate reabsorption are variable. Torsemide does not have a significant effect on glomerular filtration rate or renal blood flow. In general, diuretics worsen glucose tolerance. In addition, loop diuretics have been associated with hypercholesterolemia and hypertriglyceridemia.
 
Torsemide has a significant hemodynamic effect in patients with essential hypertension; it lowers systolic and diastolic blood pressure in patients with acute heart failure or chronic renal failure. Torsemide reduces both preload and afterload in patients with heart failure. Loop diuretics are known to induce a rise in plasma renin and this response is thought to be mediated by renal prostaglandins. A study of the effects of torsemide in 6 healthy adults on a low sodium diet indicated that up to 50% of the diuretic effect may be secondary to increased production of renal prostaglandins resulting in renal vasodilation. Before the onset of diuresis, there is a short term increase in systemic venous capacitance, an added benefit in the treatment of pulmonary edema. Patients with liver disease have high levels of aldosterone which allows accumulation of sodium in the distal convoluted tubules and collecting ducts. More efficient diuresis can be achieved in these patients by combining torsemide therapy with an aldosterone antagonist or potassium-sparing diuretic.

Pharmacokinetics

Torsemide is administered orally; an intravenous formulation was previously also commercially available. Torsemide is extensively bound to plasma proteins (greater than 99%). The volume of distribution in healthy adults, patients with mild to moderate renal failure, or patients with congestive heart failure is 12 to 15 L. Torsemide is metabolized by the hepatic cytochrome P450 isoenzyme system and is primarily a substrate of CYP2C9. In humans, three metabolites, M1, M3, and M5, are produced; only M1 and M3 have some pharmacological activity. Systemic exposures to these active metabolites are much lower compared to torsemide. In normal adults, about 80% is cleared through hepatic metabolism and 20% is cleared in the urine as unchanged drug. Following a single oral torsemide dose, the amounts of torsemide, metabolite M1, metabolite M3, and metabolite M5 recovered in the urine were 21%, 12%, 2%, and 34%, respectively. In healthy adults, the elimination half-life is about 3.5 hours.
 
Affected cytochrome P450 isoenzymes and drug transporters: CYP2C9
Torsemide is a CYP2C9 substrate and inhibitor. To a minor extent, torsemide is also a substrate of CYP2C8 and CYP2C18. Concomitant administration with a CYP2C9 inhibitor or inducer may alter the metabolism of torsemide and dosage adjustments may be necessary. Torsemide may alter serum concentrations of sensitive CYP2C9 substrates; dosage adjustments may be necessary.

Oral Route

Demadex and approved generics: Following oral administration torsemide is rapidly absorbed with about 80% bioavailability. First-pass metabolism is insignificant. Peak plasma concentration (Cmax) is achieved in about 1 hour after oral administration and is proportional to the dose. Onset of diuresis occurs within 1 hour, the peak diuretic effect occurs within 1 to 2 hours and diuresis persists for approximately 6 to 8 hours. There was a negligible increase in potassium excretion following a single 10 mg dose and a slight increase in potassium excretion of 5 to 15 mEq after a single 20 mg dose. When torsemide is taken with food, the Cmax is delayed by approximately 30 minutes, but there is no change in AUC or diuretic activity.
Soaanz: Cmax is achieved within 2.5 hours after oral administration and the AUC is proportional to the dose over a range of 2.5 mg to 200 mg. Onset of diuresis occurs within 1 hour, the peak diuretic effect occurs in the first 4 hours, and diuresis persists for approximately 6 to 8 hours. Following a single 20 mg dose in healthy adults, the mean increase in potassium excretion over 23 hours was 12.7 mEq. Administration of torsemide with a high fat, high calorie meal, delays the Cmax by 45 minutes, increases the Cmax by 100%, and increases the AUC by 48% in healthy adults; however, there is no change in overall diuretic activity.

Intravenous Route

Following IV administration, diuresis begins within 10 minutes and is maximal within 1 hour. The duration of diuresis is independent of the route of administration and lasts 6 to 8 hours.

Pregnancy And Lactation
Pregnancy

There are no data on the use of torsemide in human pregnancy and the risk of major birth defects or miscarriage. Fetal toxicity (decrease in average body weight, increase in fetal resorption, and delayed fetal ossification) occurred in pregnant rats and rabbits administered 50 and 6.8 times the human dose, respectively.

There are no data regarding the presence of torsemide in human milk or the effects of torsemide on the breast-feeding infant. Diuretics, such as torsemide, may suppress lactation as a result of intense diuresis. Previous American Academy of Pediatrics recommendations considered bendroflumethiazide, chlorthalidone, chlorothiazide, and hydrochlorothiazide as usually compatible with breast-feeding due to lack of noted adverse effects on the breast-feeding infant.