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torsemide (Demadex)

Tradename: Demadex. Indications: 1) edema associated with congestive heart failure* & hepatic or renal failure 2) hypertension used alone or in combination * torsemide is no better than furosemide in patients hospitalized with heart failure [4] * do not change loop diuretic to thiazide diuretic for hyperkalemia in patients with systolic heart failure Contraindications: - allergy to sulfomamide may result in cross-hypersensitivity Dosage: - 5-20 mg IV/PO QD - CHF: start 10-20 mg QD; max up to 200 mg QD Tabs: 5, 10, 20 mg, 100 mg. Injection: 10 mg/mL (2 mL, 5 mL) * 10-20 mg of torsemide is approximately equivalent to: furosemide 40 mg, bumetanide 1 mg Pharmacokinetics: 1) bioavailablity (oral) 80-90% 2) onset of diuresis 30-60 minutes, peak effect 1-4 hours 3) duration 6 hours 4) elimination 1/2life 2-4 hours, 7 hours with cirrhosis 5) protein binding 97-99% 6) metabolized in the liver by cyt P450 2C9 7) 20% excreted unchanged in the urine Adverse effects: 1) cardiovascular: hypotension, orthostasis 2) CNS: dizziness, headache, encephalopathy 3) dermatologic: rash, photosensitivity 4) endocrine/metabolic: - hyperglycemia, hypokalemia, hypochloremia, hyponatremia 5) gastrointestinal: cramps, nausea, vomiting 6) genitourinary: azotemia 7) hepatic: altered liver function tests 8) impaired hearing 9) renal: a) decreased uric acid secretion b) increased serum creatinine Overdose: 1) electrolyte depletion, volume depletion, hypotension, hypovolemic shock 2) GI decontamination, followed by supportive treatment Drug interactions: 1) any drug which inhibits cyt P450 2C9 can increase torsemide levels 2) any drug which induces cyt P450 2C9 can diminish torsemide levels 3) torsemide increases effects of NSAIDs 4) torsemide increases hypotensive effects of antihypertensive agents 5) torsemide increases lithium levels 6) increases risk of ototoxicity when used in combination with aminoglycosides, other loop diurectis, vancomycin 7) diuretic-induced hypokalemia increases risk of digoxin-associated arrhythmia Mechanism of action: 1) site of action: ascending loop of Henle, distal tubule 2) inhibits tubular reabsorption of Na+, Cl- 3) interferes with Cl- binding co-transport system

Interactions

drug interactions drug adverse effects (more general classes) monitor with loop diuretics

Related

cytochrome P450 2C9; cytochrome P450 BP-1; cytochrome P450 MP-4; S-mephenytoin-4-hydroxylase; limonene 6-monooxygenase; limonene 7-monooxygenase (CYP2C9, CYP2C10)

General

loop diuretic

Properties

MISC-INFO: elimination route LIVER KIDNEY pregnancy-category B safety in lactation ?

Database Correlations

PUBCHEM cid=41781

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  2. Geriatric Dosage Handbook, 6th edition, Selma et al eds, Lexi-Comp, Cleveland, 2001
  3. Medical Knowledge Self Assessment Program (MKSAP) 15, American College of Physicians, Philadelphia 2009
  4. Mentz RJ, Anstrom KJ, Eisenstein EL et al Effect of Torsemide vs Furosemide After Discharge on All-Cause Mortality in Patients Hospitalized With Heart Failure. The TRANSFORM-HF Randomized Clinical Trial. JAMA. 2023;329(3):214-223 PMID: 36648467 https://jamanetwork.com/journals/jama/fullarticle/2800428
  5. NEJM Knowledge+