DEMADEX
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DEMADEX (DEMADEX).
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.
| 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. |
| Molecular Weight | 348.42 |
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. |
| 1st trimester | Fetal risk not ruled out. Studies in animals have shown teratogenic effects, but no adequate studies in pregnant women. Use only if potential benefit justifies potential risk to the fetus. |
| 2nd trimester | May cause fetal harm. Diuretics can reduce placental perfusion and are generally avoided for gestational hypertension or preeclampsia. Use only for compelling cardiovascular indications. |
| 3rd trimester | May cause fetal harm. Potential for neonatal thrombocytopenia, electrolyte disturbances, and other adverse effects. Avoid use for edema or hypertension in pregnancy. |
Clinical note
Comprehensive clinical and safety monograph for DEMADEX (DEMADEX).
| Placental transfer | Torsemide crosses the placenta; limited data suggest fetal serum concentrations are approximately 10% of maternal concentrations. |
| Breastfeeding | Torsemide is excreted into breast milk in small amounts. The effect on the nursing infant is unknown. Caution should be exercised, and alternative diuretics (e.g., hydrochlorothiazide) may be preferred due to more data. |
■ FDA Black Box Warning
None.
| Serious Effects |
AnuriaKnown hypersensitivity to torsemide or sulfonylureasSevere electrolyte depletionHepatic coma or pre-coma
| Precautions | Hypotension and volume depletion, Electrolyte imbalances (hypokalemia, hyponatremia, hypochloremia), Ototoxicity (especially with rapid IV administration or high doses), Hyperuricemia, Sulfonamide allergy cross-reactivity |
| Food/Dietary | Avoid excessive licorice intake (glycyrrhizin) as it can exacerbate hypokalemia. Limit sodium-rich foods (processed foods, canned soups) to enhance diuretic effect and control edema. Increase potassium-rich foods (bananas, oranges, potatoes) unless on a potassium-sparing medication. Avoid grapefruit juice as it may affect metabolism. |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) |
| 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. |
| Fetal Monitoring | Monitor maternal weight, intake/output, serum electrolytes (especially potassium), BUN, creatinine, blood pressure, and uric acid. Assess fetal growth and amniotic fluid volume via ultrasound due to risk of oligohydramnios. |
| Fertility Effects | No specific human fertility studies. Animal studies at high doses showed no effect on fertility. Theoretical risk of fluid and electrolyte disturbances affecting reproductive function. |
| Clinical Pearls | DEMADEX (torsemide) is a loop diuretic with high bioavailability (80-100%) and a longer half-life (3-4 hours) than furosemide, allowing once-daily dosing. It is primarily metabolized by CYP2C9, so caution is needed with CYP2C9 inhibitors like amiodarone. Monitor for ototoxicity at high doses or rapid infusion. Hypokalemia risk persists; consider potassium supplementation or aldosterone antagonist. Use cautiously in sulfonamide allergy due to potential cross-sensitivity. |
| Patient Advice | Take DEMADEX exactly as prescribed, usually once daily in the morning to avoid nighttime urination. · Weigh yourself daily and report sudden weight gain or loss of more than 2-3 pounds in a day. · Avoid alcohol and beverages containing caffeine as they may increase dehydration. · Do not take DEMADEX with licorice (which can worsen hypokalemia) or with high-sodium antacids. · Report signs of hearing loss, ringing in the ears, dizziness, or muscle cramps immediately. · Stand up slowly to prevent dizziness from low blood pressure. · Monitor for signs of dehydration: dry mouth, thirst, infrequent urination. |