DEMADEX

Clinical safety rating: caution

Comprehensive clinical and safety monograph for DEMADEX (DEMADEX).

How it works

Inhibits the Na-K-2Cl symporter in the thick ascending limb of the loop of Henle, reducing reabsorption of sodium, chloride, and potassium, leading to increased urine output.

What the body does with it

Metabolism	Primarily hepatic via CYP450 enzymes, with minimal renal clearance.
Excretion	Approximately 50% of the absorbed dose is excreted unchanged in the urine via glomerular filtration and active tubular secretion. The remainder undergoes hepatic metabolism to glucuronide conjugates and minor oxidative metabolites, with biliary excretion of metabolites (about 30-40% of the dose) eliminated in feces. Renal clearance is the primary route for the parent drug.
Half-life	The terminal elimination half-life is approximately 4 hours (range 2-8 hours) in patients with normal renal function. In renal impairment (creatinine clearance <30 mL/min), half-life is prolonged to 10-12 hours due to reduced renal clearance. In hepatic cirrhosis, half-life may be extended to 8-9 hours due to decreased metabolism.
Protein binding	Torsemide (DEMADEX) is extensively bound to plasma proteins, primarily albumin, with a protein binding of >99%.
Volume of Distribution	The apparent volume of distribution (Vd) is approximately 0.16 L/kg (range 0.12–0.20 L/kg), indicating distribution primarily within extracellular fluid. Vd is increased in conditions with expanded extracellular volume (e.g., heart failure, cirrhosis, nephrotic syndrome).
Bioavailability	Oral bioavailability is approximately 80–90%, with minimal first-pass metabolism. Absorption is rapid and not significantly affected by food.
Onset of Action	Intravenous: Onset of diuresis occurs within 15 minutes. Oral: Onset within 30–60 minutes.
Duration of Action	Intravenous: Duration of diuretic effect is approximately 6 hours. Oral: Duration of action is 6–8 hours. The diuretic effect correlates with urinary drug concentration; prolonged use may lead to tolerance.

Classification & Brands

Dosing & administration

Oral: 5-10 mg once daily; may increase to 20 mg once daily if needed. IV: 5-10 mg once daily; may increase to 20 mg once daily if needed. Maximum dose: 40 mg/day.

Dosage form	SOLUTION
Renal impairment	GFR <20 mL/min/1.73 m²: Use with caution; may require dose reduction or discontinuation due to accumulation. GFR 20-50: No adjustment needed. GFR >50: No adjustment.
Liver impairment	Child-Pugh A: No adjustment. Child-Pugh B: Reduce dose by 50% or extend interval. Child-Pugh C: Avoid use or reduce dose by 75%.
Pediatric use	Neonates and infants: 0.1-0.2 mg/kg/dose IV/IM once daily. Children: Oral: 0.5-1 mg/kg once daily; IV/IM: 0.1-0.2 mg/kg/dose once daily. Maximum: 5 mg/day.
Geriatric use	Start at lower end of dose range (2.5-5 mg orally once daily); titrate slowly due to increased sensitivity and renal impairment risk.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for DEMADEX (DEMADEX).

Breastfeeding	Torsemide is excreted in breast milk in small amounts; M/P ratio not reported. Due to potential for diuresis, electrolyte imbalance, and allergic reactions in the infant, caution is recommended. Alternative diuretics with more safety data are preferred.
Teratogenic Risk	DEMADEX (torsemide) is a loop diuretic. Human data are limited. In animal studies, high doses caused fetal resorptions and maternal toxicity. First trimester: insufficient human data; avoid unless benefit outweighs risk. Second/third trimester: risk of fetal oligohydramnios, renal impairment, and hypovolemia; use only if clearly needed.

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Anuria","Severe electrolyte depletion","Hypersensitivity to sulfonamides or bumetanide (Demadex is a sulfonamide derivative)"]

Clinical Precautions

Precautions

["Hypotension and volume depletion","Electrolyte imbalances (hypokalemia, hyponatremia, hypochloremia)","Ototoxicity (especially with rapid IV administration or high doses)","Hyperuricemia","Sulfonamide allergy cross-reactivity"]

Clinical Tips & Counseling

Drug interactions

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DEMADEX

Clinical safety rating: caution

Comprehensive clinical and safety monograph for DEMADEX (DEMADEX).

How it works

Inhibits the Na-K-2Cl symporter in the thick ascending limb of the loop of Henle, reducing reabsorption of sodium, chloride, and potassium, leading to increased urine output.

What the body does with it

Metabolism	Primarily hepatic via CYP450 enzymes, with minimal renal clearance.
Excretion	Approximately 50% of the absorbed dose is excreted unchanged in the urine via glomerular filtration and active tubular secretion. The remainder undergoes hepatic metabolism to glucuronide conjugates and minor oxidative metabolites, with biliary excretion of metabolites (about 30-40% of the dose) eliminated in feces. Renal clearance is the primary route for the parent drug.
Half-life	The terminal elimination half-life is approximately 4 hours (range 2-8 hours) in patients with normal renal function. In renal impairment (creatinine clearance <30 mL/min), half-life is prolonged to 10-12 hours due to reduced renal clearance. In hepatic cirrhosis, half-life may be extended to 8-9 hours due to decreased metabolism.
Protein binding	Torsemide (DEMADEX) is extensively bound to plasma proteins, primarily albumin, with a protein binding of >99%.
Volume of Distribution	The apparent volume of distribution (Vd) is approximately 0.16 L/kg (range 0.12–0.20 L/kg), indicating distribution primarily within extracellular fluid. Vd is increased in conditions with expanded extracellular volume (e.g., heart failure, cirrhosis, nephrotic syndrome).
Bioavailability	Oral bioavailability is approximately 80–90%, with minimal first-pass metabolism. Absorption is rapid and not significantly affected by food.
Onset of Action	Intravenous: Onset of diuresis occurs within 15 minutes. Oral: Onset within 30–60 minutes.
Duration of Action	Intravenous: Duration of diuretic effect is approximately 6 hours. Oral: Duration of action is 6–8 hours. The diuretic effect correlates with urinary drug concentration; prolonged use may lead to tolerance.

Classification & Brands

Dosing & administration

Oral: 5-10 mg once daily; may increase to 20 mg once daily if needed. IV: 5-10 mg once daily; may increase to 20 mg once daily if needed. Maximum dose: 40 mg/day.

Dosage form	SOLUTION
Renal impairment	GFR <20 mL/min/1.73 m²: Use with caution; may require dose reduction or discontinuation due to accumulation. GFR 20-50: No adjustment needed. GFR >50: No adjustment.
Liver impairment	Child-Pugh A: No adjustment. Child-Pugh B: Reduce dose by 50% or extend interval. Child-Pugh C: Avoid use or reduce dose by 75%.
Pediatric use	Neonates and infants: 0.1-0.2 mg/kg/dose IV/IM once daily. Children: Oral: 0.5-1 mg/kg once daily; IV/IM: 0.1-0.2 mg/kg/dose once daily. Maximum: 5 mg/day.
Geriatric use	Start at lower end of dose range (2.5-5 mg orally once daily); titrate slowly due to increased sensitivity and renal impairment risk.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for DEMADEX (DEMADEX).

Breastfeeding	Torsemide is excreted in breast milk in small amounts; M/P ratio not reported. Due to potential for diuresis, electrolyte imbalance, and allergic reactions in the infant, caution is recommended. Alternative diuretics with more safety data are preferred.
Teratogenic Risk	DEMADEX (torsemide) is a loop diuretic. Human data are limited. In animal studies, high doses caused fetal resorptions and maternal toxicity. First trimester: insufficient human data; avoid unless benefit outweighs risk. Second/third trimester: risk of fetal oligohydramnios, renal impairment, and hypovolemia; use only if clearly needed.

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Anuria","Severe electrolyte depletion","Hypersensitivity to sulfonamides or bumetanide (Demadex is a sulfonamide derivative)"]