Torsemide

Pronunciation

U.S. Brand Names

Demadex®

Generic Available

Yes: Tablet

Use

Management of edema associated with congestive heart failure and hepatic or renal disease; used alone or in combination with antihypertensives in treatment of hypertension; I.V. form is indicated when rapid onset is desired

Pregnancy Risk Factor

Pregnancy Implications

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

Lactation

Excretion in breast milk unknown/use caution

Contraindications

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

Warnings/Precautions

Adjust dose to avoid dehydration. In cirrhosis, avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy. Ototoxicity is associated with rapid I.V. administration of other loop diuretics and has been seen with oral torsemide. Do not administer intravenously in less than 2 minutes; single doses should not exceed 200 mg. Hypersensitivity reactions can rarely occur. 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 is required. Monitor closely for electrolyte imbalances particularly hypokalemia and correct when necessary. Coadministration with antihypertensives may increase the risk of hypotension.

Chemical similarities are present among sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop diuretics (except ethacrynic acid). Use in patients with sulfonylurea allergy is specifically contraindicated in product labeling, however, a risk of cross-reaction exists in patients with allergy to any of these compounds; avoid use when previous reaction has been severe.

Adverse Reactions

1% to 10%:

Cardiovascular: Edema (1.1%), ECG abnormality (2%), chest pain (1.2%)

Central nervous system: Headache (7.3%), dizziness (3.2%), insomnia (1.2%), nervousness (1%)

Endocrine & metabolic: Hyperglycemia, hyperuricemia, hypokalemia

Gastrointestinal: Diarrhea (2%), constipation (1.8%), nausea (1.8%), dyspepsia (1.6%), sore throat (1.6%)

Genitourinary: Excessive urination (6.7%)

Neuromuscular & skeletal: Weakness (2%), arthralgia (1.8%), myalgia (1.6%)

Respiratory: Rhinitis (2.8%), cough increase (2%)

<1% (Limited to important or life-threatening): Syncope, atrial fibrillation, hypotension, ventricular tachycardia, shunt thrombosis, hypovolemia, GI hemorrhage, rash, rectal bleeding, angioedema, hypernatremia

Overdosage/Toxicology

Symptoms include electrolyte depletion, volume depletion, hypotension, dehydration, and circulatory collapse. Electrolyte depletion may manifest as weakness, dizziness, mental confusion, anorexia, lethargy, vomiting, and cramps. Treatment is supportive.

Drug Interactions

Substrate of CYP2C8/9 (major); Inhibits CYP2C19 (weak)

ACE inhibitors: Hypotensive effects and/or renal effects are potentiated by hypovolemia.

Aminoglycosides: Ototoxicity may be increased.

Anticoagulant activity is enhanced.

Antidiabetic agents: Glucose tolerance may be decreased.

Antihypertensive agents: Effects may be enhanced.

Beta-blockers: Plasma concentrations of beta-blockers may be increased with torsemide.

Chloral hydrate: Transient diaphoresis, hot flashes, hypertension may occur.

Cisplatin: Ototoxicity may be increased.

CYP2C8/9 inducers: May decrease the levels/effects of torsemide. Example inducers include carbamazepine, phenobarbital, phenytoin, rifampin, rifapentine, and secobarbital.

Digitalis: Arrhythmias may occur with diuretic-induced electrolyte disturbances.

Lithium: Plasma concentrations of lithium may be increased; monitor lithium levels.

NSAIDs: Torsemide efficacy may be decreased.

Probenecid: Torsemide action may be reduced.

Salicylates: Diuretic action may be impaired in patients with cirrhosis and ascites.

Thiazides: Synergistic effects may result.

Ethanol/Nutrition/Herb Interactions

Herb/Nutraceutical: Avoid dong quai if using for hypertension (has estrogenic activity). Avoid ephedra, yohimbe, ginseng (may worsen hypertension). Avoid garlic (may have increased antihypertensive effect).

Stability

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, 250 mL NS or 500 mL 0.45% sodium chloride

Compatibility

Stable in D5W, NS, ¹ /2NS

Y-site administration: Compatible: Milrinone

Mechanism of Action

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

Pharmacodynamics/Kinetics

Onset of action: Diuresis: 30-60 minutes

Peak effect: 1-4 hours

Duration: ~6 hours

Absorption: Oral: Rapid

Protein binding, plasma: ~97% to 99%

Metabolism: Hepatic (80%) via CYP

Bioavailability: 80% to 90%

Half-life elimination: 2-4; Cirrhosis: 7-8 hours

Excretion: Urine (20% as unchanged drug)

Dosage

Adults: Oral, I.V.:

Congestive heart failure: 10-20 mg once daily; may increase gradually for chronic treatment by doubling dose until the diuretic response is apparent (for acute treatment, I.V. dose may be repeated every 2 hours with double the dose as needed)

Chronic renal failure: 20 mg once daily; increase as described above

Hepatic cirrhosis: 5-10 mg once daily with an aldosterone antagonist or a potassium-sparing diuretic; increase as described above

Hypertension: 2.5-5 mg once daily; increase to 10 mg after 4-6 weeks if an adequate hypotensive response is not apparent; if still not effective, an additional antihypertensive agent may be added

Administration

I.V. injections should be administered over

2 minutes; the oral form may be administered regardless of meal times; patients may be switched from the I.V. form to the oral and vice-versa with no change in dose; no dosage adjustment is needed in the elderly or patients with hepatic impairment

To administer as a continuous infusion: 50 mg or 200 mg torsemide should be diluted in 250 mL or 500 mL of compatible solution in plastic containers

Monitoring Parameters

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

Patient Education

Inform prescriber of all prescriptions, OTC medications, or herbal products you are taking, and any allergies you have. Do not take any new medication during therapy unless approved by prescriber. Take as directed, with food or milk (to reduce GI distress), early in the day, or if twice daily, take last dose in late afternoon in order to avoid sleep disturbance and achieve maximum therapeutic effect. Include orange juice or bananas (or other potassium-rich foods) in daily diet. Do not take potassium supplements without consulting prescriber. Weigh yourself each day, at the same time, in the same clothes when beginning therapy, and weekly on long-term therapy; report unusual or unanticipated weight gain or loss. May cause postural hypotension (change position slowly when rising from sitting or lying); transient drowsiness, blurred vision, or dizziness (avoid driving or engaging in tasks that require alertness until response to drug is known); reduced tolerance to heat (avoid strenuous activity in hot weather or excessively hot showers); or constipation (increased exercise and increased dietary fiber, fruit, or fluids may help). Report unusual weight gain or loss (>5 lb/week), swelling of ankles and hands; persistent fatigue; unresolved constipation or diarrhea; weakness, fatigue, or dizziness; vomiting; cramps; change in hearing; or chest pain or palpitations. Breast-feeding precaution: Consult prescriber if breast-feeding.

Additional Information

10-20 mg torsemide is approximately equivalent to furosemide 40 mg or bumetanide 1 mg.

Anesthesia and Critical Care Concerns/Other Considerations

If given the morning of surgery, it may render the patient volume depleted and blood pressure may be labile during general anesthesia. Torsemide may induce potent diuretic effects and, as with other potent diuretics, electrolytes and volume status needs to be closely monitored.

Equivalent dosing: Torsemide 10-20 mg is approximately equivalent to furosemide 40 mg or bumetanide 1 mg.

Cardiovascular Considerations

Torsemide may induce potent diuretic effects and, as with other potent diuretics, electrolytes and volume status needs to be closely monitored.

Dental Health: Effects on Dental Treatment

No significant effects or complications reported

Dental Health: Vasoconstrictor/Local Anesthetic Precautions

No information available to require special precautions

Mental Health: Effects on Mental Status

May cause dizziness

Mental Health: Effects on Psychiatric Treatment

May cause agranulocytosis; use caution with clozapine and carbamazepine; may decrease lithium clearance resulting in an increase in serum lithium levels and potential lithium toxicity, however, this is much more common and significant with the thiazide diuretics; monitor serum lithium levels; concurrent use with chloral hydrate may produce hot flashes and hypertension

Dosage Forms

Injection, solution: 10 mg/mL (2 mL, 5 mL)

Tablet: 5 mg, 10 mg, 20 mg, 100 mg

References

Chobanian AV, Bakris GL, Black HR, et al, "The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 Report," JAMA , 2003, 289(19):2560-71.

Hariman RJ, Bremner S, Louie EK, et al, "Dose-Response Study of Intravenous Torsemide in Congestive Heart Failure," Am Heart J , 1994, 128(2):352-7.

Hunt SA, Baker DW, Chin MH, et al, "ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult: Executive Summary. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and Management of Heart Failure)," J Am Coll Cardiol , 2001, 38(7):2101-13.

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