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Torsemide

Pronunciation

Pronunciation

(TORE se mide)

Index Terms

  • Demadex
  • Torasemide

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Intravenous:

Generic: 20 mg/2 mL (2 mL [DSC]); 50 mg/5 mL (5 mL [DSC])

Tablet, Oral:

Demadex: 5 mg, 10 mg, 20 mg, 100 mg [DSC] [scored]

Generic: 5 mg, 10 mg, 20 mg, 100 mg

Brand Names: U.S.

  • Demadex

Pharmacologic Category

  • Antihypertensive
  • Diuretic, Loop

Pharmacology

Inhibits reabsorption of sodium and chloride in the ascending loop of Henle and distal renal tubule, interfering with the chloride-binding cotransport system, thus causing increased excretion of water, sodium, chloride, magnesium, and calcium; does not alter GFR, renal plasma flow, or acid-base balance

Absorption

Oral: Rapid

Distribution

Vd: 12-15 L; Cirrhosis: Approximately doubled

Metabolism

Hepatic (~80%) via CYP

Excretion

Urine (~20% as unchanged drug)

Onset of Action

Diuresis: Oral: Within 1 hour; IV: 10 minutes; Peak effect: Diuresis: Oral: 1-2 hours; IV: Within 60 minutes; Antihypertensive: Oral: 4-6 weeks (up to 12 weeks)

Time to Peak

Plasma: Oral: 1 hour; delayed ~30 minutes when administered with food

Duration of Action

Diuresis: Oral, IV: ~6-8 hours

Half-Life Elimination

~3.5 hours; Cirrhosis: 7-8 hours

Protein Binding

Plasma: >99%

Special Populations: Renal Function Impairment

Renal clearance is decreased, but total plasma clearance is not significantly altered.

Special Populations: Hepatic Function Impairment

In patients with hepatic cirrhosis, the Vd, plasma t½, and renal clearance are all increased, but total clearance is not changed.

Special Populations: Elderly

There may be a decrease in renal clearance related to the decline in renal function that commonly occurs with aging.

Special Populations Note

Decompensated Heart Failure: Hepatic and renal clearance are decreased with oral administration.

Use: Labeled Indications

Management of edema associated with heart failure and hepatic or renal disease (including chronic renal failure); treatment of hypertension

Note: According to the Eighth Joint National Committee (JNC 8) guidelines, loop diuretics are not recommended for the initial treatment of hypertension (James, 2013). In patients with chronic kidney disease (ie, eGFR <30 mL/minute/1.73 m2), the American Society of Hypertension/International Society of Hypertension (ASH/ISH) suggests that the use of a loop diuretic may be necessary (Weber, 2014).

Contraindications

Hypersensitivity to torsemide, any component of the formulation, or any sulfonylurea; anuria

Dosing: Adult

Note: IV and oral dosing are equivalent. Dose equivalency for patients with normal renal function (approximate): Torsemide 20 mg = Bumetanide 1 mg = furosemide 40 mg = ethacrynic acid 50 mg

Edema:

Chronic renal failure: Oral, IV: Initial: 20 mg once daily; may increase gradually by doubling dose until the desired diuretic response is obtained (maximum recommended daily dose: 200 mg)

Heart failure:

Oral: Initial: 10 to 20 mg once daily; may increase gradually by doubling dose until the desired diuretic response is obtained. Note: ACCF/AHA 2013 guidelines for heart failure maximum recommended daily dose: 200 mg (Yancy, 2013).

IV: Initial: 10 to 20 mg; may repeat every 2 hours with double the dose as needed.

Continuous IV infusion (off-label dose): Initial: 20 mg IV load, then 5 to 20 mg/hour; repeat loading dose before increasing infusion rate. Note: With lower baseline creatinine clearance (eg, CrCl <25 mL/minute), the upper end of the initial infusion dosage range should be considered (ACCF/AHA [Yancy, 2013]; Brater, 1998)

Hepatic cirrhosis: Oral: Initial: 5 to 10 mg once daily; may increase gradually by doubling dose until the desired diuretic response is obtained (maximum recommended single dose: 40 mg). Note: Administer with an aldosterone antagonist or a potassium-sparing diuretic.

Hypertension: Oral: Initial: 5 mg once daily; may increase to 10 mg once daily after 4 to 6 weeks if adequate antihypertensive response is not apparent; if still not effective, an additional antihypertensive agent may be added. Usual dosage range (ASH/ISH [Weber, 2014]): 10 mg daily.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment

No dosage adjustment necessary. However, higher doses may be required to achieve diuretic response.

Dosing: Hepatic Impairment

There are no dosage adjustments provided in manufacturer’s labeling; use with caution.

Administration

IV: Administer over ≥2 minutes; reserve IV administration for situations which require rapid onset of action

Oral: Administer without regard to meals; patients may be switched from the IV form to the oral (and vice-versa) with no change in dose

Dietary Considerations

May be taken without regard to meals; however, food slows the rate and reduces the extent of absorption and may reduce diuretic efficacy (Bard, 2004). May require increased intake of potassium-rich foods.

Compatibility

Stable in D5W, NS, 1/2NS.

Storage

IV: Store at 15°C to 30°C (59°F to 86°F). If torsemide is to be administered via continuous infusion, stability has been demonstrated through 24 hours at room temperature in plastic containers for the following fluids and concentrations:

200 mg torsemide (10 mg/mL) added to 250 mL D5W, 250 mL NS or 500 mL 0.45% sodium chloride

50 mg torsemide (10 mg/mL) added to 500 mL D5W, 500 mL NS, or 500 mL 0.45% sodium chloride

Tablets: Store at 15°C to 30°C (59°F to 86°F).

Drug Interactions

ACE Inhibitors: Loop Diuretics may enhance the hypotensive effect of ACE Inhibitors. Loop Diuretics may enhance the nephrotoxic effect of ACE Inhibitors. Monitor therapy

Ajmaline: Sulfonamides may enhance the adverse/toxic effect of Ajmaline. Specifically, the risk for cholestasis may be increased. Monitor therapy

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Allopurinol: Loop Diuretics may enhance the adverse/toxic effect of Allopurinol. Loop Diuretics may increase the serum concentration of Allopurinol. Specifically, Loop Diuretics may increase the concentration of Oxypurinol, an active metabolite of Allopurinol. Monitor therapy

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification

Aminoglycosides: Loop Diuretics may enhance the adverse/toxic effect of Aminoglycosides. Specifically, nephrotoxicity and ototoxicity. Monitor therapy

Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Analgesics (Opioid): May enhance the adverse/toxic effect of Diuretics. Analgesics (Opioid) may diminish the therapeutic effect of Diuretics. Monitor therapy

Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Beta2-Agonists: May enhance the hypokalemic effect of Loop Diuretics. Monitor therapy

Bile Acid Sequestrants: May decrease the absorption of Loop Diuretics. Consider therapy modification

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Canagliflozin: May enhance the hypotensive effect of Loop Diuretics. Management: If canagliflozin is combined with a loop diuretic, monitor for symptoms of intravascular volume depletion and hypotension. Canadian product labeling recommends avoiding the combination of canagliflozin and loop diuretics. Consider therapy modification

Cardiac Glycosides: Loop Diuretics may enhance the adverse/toxic effect of Cardiac Glycosides. Specifically, cardiac glycoside toxicity may be enhanced by the hypokalemic and hypomagnesemic effect of loop diuretics. Monitor therapy

Cefazedone: May enhance the nephrotoxic effect of Loop Diuretics. Monitor therapy

Cefotiam: Loop Diuretics may enhance the nephrotoxic effect of Cefotiam. Monitor therapy

Ceftizoxime: Loop Diuretics may enhance the nephrotoxic effect of Ceftizoxime. Monitor therapy

Cephalothin: Loop Diuretics may enhance the nephrotoxic effect of Cephalothin. Monitor therapy

Cephradine: May enhance the nephrotoxic effect of Loop Diuretics. Monitor therapy

Ceritinib: May increase the serum concentration of CYP2C9 Substrates. Management: Concurrent use of ceritinib with a CYP2C9 substrate that has a narrow therapeutic index (e.g., warfarin, phenytoin) should be avoided when possible. Monitor therapy

CISplatin: Loop Diuretics may enhance the nephrotoxic effect of CISplatin. Loop Diuretics may enhance the ototoxic effect of CISplatin. Monitor therapy

Corticosteroids (Orally Inhaled): May enhance the hypokalemic effect of Loop Diuretics. Monitor therapy

Corticosteroids (Systemic): May enhance the hypokalemic effect of Loop Diuretics. Monitor therapy

CycloSPORINE (Systemic): May enhance the adverse/toxic effect of Loop Diuretics. Monitor therapy

CYP2C9 Inducers (Strong): May increase the metabolism of CYP2C9 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

CYP2C9 Inhibitors (Moderate): May decrease the metabolism of CYP2C9 Substrates. Monitor therapy

CYP2C9 Inhibitors (Strong): May decrease the metabolism of CYP2C9 Substrates. Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP2C9 Substrates. Management: Seek alternatives to the CYP2C9 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Dofetilide: Loop Diuretics may enhance the QTc-prolonging effect of Dofetilide. Monitor therapy

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy

Eltrombopag: May increase the serum concentration of OATP1B1/SLCO1B1 Substrates. Monitor therapy

Empagliflozin: May enhance the hypotensive effect of Loop Diuretics. Monitor therapy

Enzalutamide: May decrease the serum concentration of CYP2C9 Substrates. Management: Concurrent use of enzalutamide with CYP2C9 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP2C9 substrate should be performed with caution and close monitoring. Consider therapy modification

Foscarnet: Loop Diuretics may increase the serum concentration of Foscarnet. Consider therapy modification

Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Ivabradine: Loop Diuretics may enhance the arrhythmogenic effect of Ivabradine. Monitor therapy

Levodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa. Monitor therapy

Levosulpiride: Loop Diuretics may enhance the adverse/toxic effect of Levosulpiride. Avoid combination

Licorice: May enhance the hypokalemic effect of Loop Diuretics. Monitor therapy

Lithium: Loop Diuretics may decrease the serum concentration of Lithium. Loop Diuretics may increase the serum concentration of Lithium. Monitor therapy

Lumacaftor: May decrease the serum concentration of CYP2C9 Substrates. Lumacaftor may increase the serum concentration of CYP2C9 Substrates. Monitor therapy

Mecamylamine: Sulfonamides may enhance the adverse/toxic effect of Mecamylamine. Avoid combination

Methotrexate: May diminish the therapeutic effect of Loop Diuretics. Loop Diuretics may increase the serum concentration of Methotrexate. Methotrexate may increase the serum concentration of Loop Diuretics. Management: Monitor for increased methotrexate and/or loop diuretic levels/toxicity with concomitant use of these agents and monitor for decreased therapeutic effects of loop diuretics. Methotrexate and/or loop diuretic dose reductions may be necessary. Consider therapy modification

Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

MiFEPRIStone: May increase the serum concentration of CYP2C9 Substrates. Management: Use CYP2C9 substrates at the lowest recommended dose, and monitor closely for adverse effects, during and in the 2 weeks following mifepristone treatment. Consider therapy modification

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Neuromuscular-Blocking Agents: Loop Diuretics may diminish the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Loop Diuretics may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: May diminish the diuretic effect of Loop Diuretics. Loop Diuretics may enhance the nephrotoxic effect of Nonsteroidal Anti-Inflammatory Agents. Management: Monitor for evidence of kidney injury or decreased therapeutic effects of loop diuretics with concurrent use of an NSAID. Consider avoiding concurrent use in CHF or cirrhosis. Concomitant use of bumetanide with indomethacin is not recommended. Consider therapy modification

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Consider therapy modification

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Probenecid: May enhance the adverse/toxic effect of Loop Diuretics. Probenecid may diminish the diuretic effect of Loop Diuretics. Probenecid may increase the serum concentration of Loop Diuretics. Management: Monitor for decreased diuretic effects or increased adverse effects of loop diuretics with concomitant use of probenecid. Bumetanide prescribing information recommends against concomitant use of probenecid. Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Reboxetine: May enhance the hypokalemic effect of Loop Diuretics. Monitor therapy

RisperiDONE: Loop Diuretics may enhance the adverse/toxic effect of RisperiDONE. Management: Consider alternative diuretic therapy (e.g., thiazides) to more potent diuretics (e.g., furosemide) in elderly patients receiving risperidone. Patients who require use of more potent diuretic therapy should be closely monitored and adequately hydrated. Consider therapy modification

Salicylates: May diminish the diuretic effect of Loop Diuretics. Loop Diuretics may increase the serum concentration of Salicylates. Monitor therapy

Sodium Phosphates: Diuretics may enhance the nephrotoxic effect of Sodium Phosphates. Specifically, the risk of acute phosphate nephropathy may be enhanced. Management: Consider avoiding this combination by temporarily suspending treatment with diuretics, or seeking alternatives to oral sodium phosphate bowel preparation. If the combination cannot be avoided, hydrate adequately and monitor fluid and renal status. Consider therapy modification

Teriflunomide: May increase the serum concentration of OATP1B1/SLCO1B1 Substrates. Monitor therapy

Tobramycin (Oral Inhalation): Loop Diuretics may enhance the nephrotoxic effect of Tobramycin (Oral Inhalation). Loop Diuretics may enhance the ototoxic effect of Tobramycin (Oral Inhalation). Monitor therapy

Topiramate: Loop Diuretics may enhance the hypokalemic effect of Topiramate. Monitor therapy

Warfarin: Torsemide may increase the serum concentration of Warfarin. Monitor therapy

Yohimbine: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Adverse Reactions

1% to 10%:

Cardiovascular: ECG abnormality (2%), chest pain (1%)

Central nervous system: Nervousness (1%)

Gastrointestinal: Constipation (2%), diarrhea (2%), dyspepsia (2%), nausea (2%), sore throat (2%)

Genitourinary: Excessive urination (7%)

Neuromuscular & skeletal: Arthralgia (2%), myalgia (2%), weakness (2%)

Respiratory: Rhinitis (3%), cough (2%)

<1% (Limited to important or life-threatening): Angioedema, arthritis, atrial fibrillation, esophageal hemorrhage, GI hemorrhage, hyperglycemia, hyperuricemia, hypokalemia, hyponatremia, hypotension, hypovolemia, impotence, leukopenia, pancreatitis, rash, rectal bleeding, shunt thrombosis, Stevens-Johnson syndrome, syncope, thirst, thrombocytopenia, toxic epidermal necrolysis, ventricular tachycardia, vomiting

Warnings/Precautions

Concerns related to adverse effects:

• Fluid/electrolyte loss: Loop diuretics are potent diuretics; excess amounts can lead to profound diuresis with fluid and electrolyte loss; close medical supervision and dose evaluation are required. Potassium supplementation and/or use of potassium-sparing diuretics may be necessary to prevent hypokalemia. In contrast to thiazide diuretics, a loop diuretic can also lower serum calcium concentrations. Electrolyte disturbances can predispose a patient to serious cardiac arrhythmias.

• Nephrotoxicity: Monitor fluid status and renal function in an attempt to prevent oliguria, azotemia, and reversible increases in BUN and creatinine; close medical supervision of aggressive diuresis required.

• Ototoxicity: Ototoxicity has been demonstrated following oral administration of torsemide and following rapid IV administration of other loop diuretics. Other possible risk factors may include use in renal impairment, excessive doses, and concurrent use of other ototoxins (eg, aminoglycosides).

• Sulfonamide (“sulfa”) allergy: The FDA-approved product labeling for many medications containing a sulfonamide chemical group includes a broad contraindication in patients with a prior allergic reaction to sulfonamides. There is a potential for cross-reactivity between members of a specific class (eg, two antibiotic sulfonamides). However, concerns for cross-reactivity have previously extended to all compounds containing the sulfonamide structure (SO2NH2). An expanded understanding of allergic mechanisms indicates cross-reactivity between antibiotic sulfonamides and nonantibiotic sulfonamides may not occur or at the very least this potential is extremely low (Brackett 2004; Johnson 2005; Slatore 2004; Tornero 2004). In particular, mechanisms of cross-reaction due to antibody production (anaphylaxis) are unlikely to occur with nonantibiotic sulfonamides. T-cell-mediated (type IV) reactions (eg, maculopapular rash) are less well understood and it is not possible to completely exclude this potential based on current insights. In cases where prior reactions were severe (Stevens-Johnson syndrome/TEN), some clinicians choose to avoid exposure to these classes.

Disease-related concerns:

• Cirrhosis: Use with caution in patients with cirrhosis; avoid sudden changes in fluid and electrolyte balance and acid/base status which may lead to hepatic encephalopathy. Administration with an aldosterone antagonist or potassium-sparing diuretic may provide additional diuretic efficacy and maintain normokalemia.

Concurrent drug therapy issues:

• Antihypertensives: Coadministration of antihypertensives may increase the risk of hypotension.

Special populations:

• Surgical patients: If given the morning of surgery, torsemide may render the patient volume depleted and blood pressure may be labile during general anesthesia.

Other warnings and precautions:

• Diuretic resistance: For some patients, despite higher doses of loop diuretic treatment, an adequate diuretic response cannot be attained. Diuretic resistance can usually be overcome by intravenous administration, the use of two diuretics together (eg, furosemide and chlorothiazide), or the use of a diuretic with a positive inotropic agent. When such combinations are used, serum electrolytes need to be monitored even more closely (Cody, 1994; ACC/AHA [Yancy, 2013]; HFSA, 2010).

Monitoring Parameters

Renal function, electrolytes, and fluid status (weight and I & O), blood pressure

Pregnancy Risk Factor

B

Pregnancy Considerations

A decrease in fetal weight, an increase in fetal resorption, and delayed fetal ossification has occurred in animal studies.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience headache. Have patient report immediately to prescriber signs of fluid and electrolyte problems (mood changes, confusion, muscle pain or weakness, abnormal heartbeat, very bad dizziness or passing out, fast heartbeat, more thirst, seizures, feeling very tired or weak, not hungry, unable to pass urine or change in the amount of urine produced, dry mouth, dry eyes, or nausea or vomiting), signs of high blood sugar (confusion, feeling sleepy, more thirst, hunger, passing urine more often, flushing, fast breathing, or breath that smells like fruit), signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), severe dizziness, passing out, severe diarrhea, hearing impairment, tinnitus, or shortness of breath (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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