DIULO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DIULO (DIULO).
Inhibits the Na+/Cl- symporter in the distal convoluted tubule of the nephron, reducing reabsorption of sodium and chloride, leading to increased diuresis and decreased extracellular fluid volume.
| Metabolism | Primarily hepatic via CYP450 enzymes; minimal first-pass metabolism. |
| Excretion | Primarily renal excretion (60-70% as unchanged drug) via glomerular filtration and tubular secretion; approximately 10-15% biliary/fecal elimination. |
| Half-life | Terminal elimination half-life is 1.5-2 hours (mean 1.8 h) in healthy adults; prolonged to 3-6 hours in renal impairment and up to 8 hours in severe heart failure. |
| Protein binding | 95-99% bound to albumin and alpha-1-acid glycoprotein specific; binding is saturable at high concentrations. |
| Volume of Distribution | 0.13-0.25 L/kg (average 0.2 L/kg) indicating distribution largely within extracellular fluid; Vd increases in edema states. |
| Bioavailability | Oral bioavailability is 60-70% due to first-pass metabolism; approximately 50% in patients with severe heart failure or edema. |
| Onset of Action | Oral: Approximately 1 hour after dosing; peak effect at 1-2 hours. Intravenous: within 5 minutes; peak effect at 30 minutes. |
| Duration of Action | Oral: 4-6 hours; IV: 2-3 hours. Duration may be prolonged in renal impairment or with high dosing. |
2.5 mg orally once daily, may increase to 5 mg once daily after 4 weeks if needed.
| Dosage form | TABLET |
| Renal impairment | eGFR 30-59 mL/min: no adjustment; eGFR 15-29 mL/min: 2.5 mg once daily; eGFR <15 mL/min or on dialysis: not recommended. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B or C: not recommended due to lack of data. |
| Pediatric use | Not approved for pediatric patients. |
| Geriatric use | Start at 2.5 mg once daily; monitor renal function and electrolytes closely. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DIULO (DIULO).
| Breastfeeding | Unknown if excreted in human milk. No M/P ratio available. Considered compatible with breastfeeding by most authorities due to low oral bioavailability in infants, but monitor for hypotension, electrolyte disturbances, and decreased milk production. |
| Teratogenic Risk | No adequate studies in pregnant women. Based on animal data, may cause fetal harm. First trimester: possible teratogenic effects (limb defects, CNS malformations). Second/third trimester: risk of fetal hypotension, oligohydramnios, renal impairment, skull ossification defects. Avoid use unless benefit outweighs risk. |
■ FDA Black Box Warning
None
| Serious Effects |
["Anuria","Renal failure","Hepatic coma or pre-coma","Hypersensitivity to sulfonamide-derived drugs","Severe electrolyte abnormalities"]
| Precautions | ["Hypokalemia","Hyperuricemia","Hypomagnesemia","Hyperglycemia","Hypercalcemia","Sulfonamide allergy cross-reactivity","Excessive diuresis leading to volume depletion and electrolyte imbalance"] |
| Food/Dietary | Avoid excessive intake of high-potassium foods (e.g., bananas, oranges, potatoes) unless directed. Avoid salt substitutes containing potassium. Grapefruit juice may increase metolazone levels; limit consumption. Avoid alcohol as it may potentiate orthostatic hypotension. |
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| Fetal Monitoring |
| Monitor maternal blood pressure, renal function (BUN, creatinine), electrolytes (particularly potassium), and urine output. Fetal monitoring with ultrasound for growth, amniotic fluid volume, and renal function (umbilical artery Doppler if growth restriction occurs). |
| Fertility Effects | No data on human fertility. In animal studies, no impairment of fertility observed. May theoretically affect spermatogenesis or ovulation due to changes in renal blood flow and electrolyte balance, but clinical significance unknown. |
| Clinical Pearls |
| Diulo (metolazone) is a thiazide-like diuretic used for hypertension and edema. Its long half-life allows once-daily dosing. Monitor for hypokalemia, hyponatremia, and hyperuricemia. Synergistic effect when used with loop diuretics for refractory edema. Avoid in severe renal impairment (CrCl <20 mL/min). |
| Patient Advice | Take exactly as prescribed, usually once daily. · May cause increased urination; take in morning to avoid nighttime disruption. · Avoid alcohol and NSAIDs unless approved by your doctor. · Report signs of electrolyte imbalance: muscle cramps, weakness, irregular heartbeat. · Monitor blood pressure regularly. · Avoid prolonged sun exposure; use sunscreen due to photosensitivity risk. · Do not stop abruptly without consulting your doctor. |