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Medication Safety Issues
Sound-alike/look-alike issues:
Torsemide may be confused with furosemide
Demadex® may be confused with Denorex®
Pronunciation
(TORE se mide)
U.S. Brand Names
Generic Available
Yes: Tablet
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Management of edema associated with 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
B
Pregnancy Considerations
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
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. Watch for and correct electrolyte disturbances; adjust dose to avoid dehydration.
• 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: Rapid I.V. administration (associated with other loop diuretics), renal impairment, excessive doses, and concurrent use of other ototoxins is associated with ototoxicity; has been seen with oral torsemide.
• Sulfa allergy: 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. Discontinue if signs of hypersensitivity are noted.
Disease-related concerns:
• Cirrhosis: In cirrhosis, avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy.
Concurrent drug therapy issues:
• Antihypertensives: Coadministration of antihypertensives may increase the risk of hypotension.
Adverse Reactions
1% to 10%:
Cardiovascular: ECG abnormality (2%), edema (1.1%), 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
Metabolism/Transport Effects
Substrate of CYP2C8 (minor), 2C9 (major); Inhibits CYP2C19 (weak)
Drug Interactions
ACE Inhibitors: Loop Diuretics may enhance the hypotensive effect of ACE Inhibitors. Specifically, postural hypotension which can accompany ACE Inhibitor initiation. Loop Diuretics may enhance the nephrotoxic effect of ACE Inhibitors. Risk C: 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 Oxypurinolol, an active metabolite of Allopurinol. Risk C: Monitor therapy
Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification
Aminoglycosides: Loop Diuretics may enhance the adverse/toxic effect of Aminoglycosides. Specifically, nephrotoxicity and ototoxicity. Risk C: Monitor therapy
Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy
Bile Acid Sequestrants: May decrease the absorption of Loop Diuretics. Risk D: Consider therapy modification
Corticosteroids (Orally Inhaled): May enhance the hypokalemic effect of Loop Diuretics. Risk C: Monitor therapy
Corticosteroids (Systemic): May enhance the hypokalemic effect of Loop Diuretics. Risk C: Monitor therapy
CYP2C9 Inducers (Highly Effective): May increase the metabolism of CYP2C9 Substrates (High risk). Risk C: Monitor therapy
CYP2C9 Inhibitors (Moderate): May decrease the metabolism of CYP2C9 Substrates (High risk). Risk C: Monitor therapy
CYP2C9 Inhibitors (Strong): May decrease the metabolism of CYP2C9 Substrates (High risk). Risk D: Consider therapy modification
Diazoxide: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Dofetilide: Loop Diuretics may enhance the QTc-prolonging effect of Dofetilide. Risk C: Monitor therapy
Eltrombopag: May increase the serum concentration of OATP1B1/SLCO1B1 Substrates. Management: According to eltrombopag prescribing information, consideration of a preventative dose reduction may be warranted. Risk D: Consider therapy modification
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Hypotensive Agents: May enhance the adverse/toxic effect of other Hypotensive Agents. Risk C: Monitor therapy
Lithium: Loop Diuretics may decrease the serum concentration of Lithium. Loop Diuretics may increase the serum concentration of Lithium. Risk C: Monitor therapy
MAO Inhibitors: May enhance the orthostatic effect of Orthostasis Producing Agents. Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: 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. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May diminish the diuretic effect of Loop Diuretics. Risk C: Monitor therapy
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2C9 Substrates (High risk). Risk C: Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Phenytoin: May diminish the diuretic effect of Loop Diuretics. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification
Salicylates: May diminish the diuretic effect of Loop Diuretics. Loop Diuretics may increase the serum concentration of Salicylates. Risk C: Monitor therapy
Warfarin: Torsemide may increase the serum concentration of Warfarin. Risk C: Monitor therapy
Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Herb/Nutraceutical: Avoid herbs with hypertensive properties (bayberry, blue cohosh, cayenne, ephedra, ginger, ginseng [American], kola, licorice); may diminish the antihypertensive effect of torsemide. Avoid herbs with hypotensive properties (black cohosh, California poppy, coleus, golden seal, hawthorn, mistletoe, periwinkle, quinine, shepherd's purse); may enhance the hypotensive effect of torsemide.
Storage
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.:
Chronic renal failure: 20 mg once daily; increase as described above
Heart failure: Initial: 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). Note: ACC/AHA 2009 guidelines for heart failure recommend a maximum daily oral dose of 200 mg; maximum single I.V. dose of 100-200 mg
Continuous I.V. infusion (Hunt, 2009): 20 mg I.V. load then 5-20 mg/hour
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.
I.V. injections should be given over ?2 minutes.
Administration: I.V. Detail
Ototoxicity has occurred with too rapid of injection.
pH: >8.3
Monitoring Parameters
Renal function, electrolytes, and fluid status (weight and I & O), blood pressure
Patient Education
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.
Geriatric Considerations
Loop diuretics are potent diuretics, excess amounts can lead to profound diuresis with fluid and electrolyte loss. Close medical supervision and dose evaluation is required, particularly in elderly.
Additional Information
10-20 mg torsemide is approximately equivalent to furosemide 40 mg or bumetanide 1 mg.
Anesthesia and Critical Care Concerns/Other Considerations
Clinical Pearls/Comments: 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.
Dose equivalency (approximate): Bumetanide 1 mg = furosemide 40 mg = torsemide 10 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
Nursing: Physical Assessment/Monitoring
Assess for allergy to sulfonylurea before beginning therapy. Assess potential for interactions with other pharmacological agents or herbal products the patient may be taking (especially anything that may impact fluid balance or increase potential for ototoxicity or hypotension). For intravenous use, see Administration specifics. Assess results of laboratory tests (electrolytes), therapeutic effectiveness, and adverse response (eg, dehydration, electrolyte imbalance, postural hypotension) on a regular basis during therapy. Caution patients with diabetes about closely monitoring glucose levels (glucose tolerance may be decreased). Teach patient appropriate use, possible side effects/appropriate interventions, and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Injection, solution:
Demadex®: 10 mg/mL (2 mL [DSC], 5 mL [DSC])
Tablet: 5 mg, 10 mg, 20 mg, 100 mg
Demadex®: 5 mg, 10 mg, 20 mg, 100 mg [scored]
Pricing: U.S. (www.drugstore.com)
Tablets (Demadex)
5 mg (30): $41.39
10 mg (30): $43.69
20 mg (30): $49.44
100 mg (30): $160.98
Tablets (Torsemide)
5 mg (30): $18.99
10 mg (30): $19.99
20 mg (30): $22.99
100 mg (30): $75.98
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, Abraham WT, Chin MH, et al, “2009 Focused Update Incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the International Society for Heart and Lung Transplantation,” J Am Coll Cardiol, 2009, 53(15):e1-e90.
International Brand Names
Lexi-Comp.com
Last full review/revision September 2009
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