XTRELUS
Clinical safety rating: caution
Comprehensive clinical and safety monograph for XTRELUS (XTRELUS).
Selective inhibitor of the sodium-glucose cotransporter 2 (SGLT2) in the proximal renal tubules, reducing glucose reabsorption and lowering blood glucose levels.
| Metabolism | Primarily metabolized via glucuronidation by UGT1A9 and UGT2B7; minor CYP metabolism (CYP3A4). |
| Excretion | Renal excretion accounts for approximately 65% of the administered dose as unchanged drug, with an additional 20% as metabolites. Biliary/fecal excretion accounts for the remaining 15%, primarily as metabolites. |
| Half-life | The terminal elimination half-life is approximately 12 hours in patients with normal renal function. In patients with moderate renal impairment (CrCl 30-50 mL/min), half-life is prolonged to 20-24 hours, necessitating dose adjustment. |
| Protein binding | Approximately 92% bound to serum albumin. Binding is saturable and reduced in hypoalbuminemia (e.g., liver disease, nephrotic syndrome). |
| Volume of Distribution | The volume of distribution is approximately 1.5 L/kg. This value indicates extensive extravascular distribution, likely into total body water and tissues, consistent with moderate lipophilicity. |
| Bioavailability | Oral bioavailability is approximately 75% (range 65-85%) due to first-pass metabolism, primarily by CYP3A4. Food reduces the rate but not the extent of absorption. |
| Onset of Action | Oral administration: Clinical effects appear within 1-2 hours; peak plasma concentration achieved at 2-4 hours. Intravenous administration: Onset is within 10-15 minutes. |
| Duration of Action | Duration of therapeutic effect is approximately 8-12 hours after oral administration, correlating with plasma concentration above the minimum effective concentration. Prolonged to 12-18 hours in renal impairment. |
| Molecular Weight | 467.5 |
XTRELUS (luseogliflozin) 2.5 mg orally once daily, increased to 5 mg once daily if needed.
| Dosage form | TABLET |
| Renal impairment | eGFR ≥60 mL/min/1.73 m²: no adjustment. eGFR 45-59: use 2.5 mg once daily. eGFR <45: contraindicated. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B or C: not recommended due to limited data. |
| Pediatric use | Safety and efficacy not established in pediatric patients (<18 years). |
| Geriatric use | No dose adjustment based on age alone. Monitor renal function and volume status due to higher risk of dehydration and hypotension. |
| 1st trimester | Human data limited; animal studies show developmental toxicity; avoid unless benefit clearly outweighs risk. |
| 2nd trimester | May cause fetal harm if used during organogenesis; risk of teratogenicity; avoid use. |
| 3rd trimester | Potential for adverse effects on fetal growth and development; avoid in third trimester unless no alternative. |
Clinical note
Comprehensive clinical and safety monograph for XTRELUS (XTRELUS).
| Placental transfer | Extensively crosses placenta; fetal blood concentrations approximate maternal levels. |
| Breastfeeding | Excreted in breast milk in low concentrations; potential for serious adverse reactions in nursing infants; discontinue breastfeeding or drug based on importance to mother. |
| Lactation Rating |
■ FDA Black Box Warning
None
| Serious Effects |
PregnancyHypersensitivity to Xtrelus or any excipient
| Precautions | Hypotension, Ketoacidosis, Acute kidney injury, Urosepsis and pyelonephritis, Hypoglycemia when used with insulin or insulin secretagogues, Necrotizing fasciitis of the perineum (Fournier's gangrene), Genital mycotic infections, Increased LDL-cholesterol, Volume depletion |
| Food/Dietary | Avoid grapefruit and grapefruit juice due to CYP3A4 inhibition increasing lixivaptan exposure. No other significant food interactions known. Advise patients to maintain consistent fluid intake and avoid excessive water consumption. |
| Clinical Pearls |
Loading safety data…
| L4 - Possibly Hazardous |
| Teratogenic Risk | Contraindicated in pregnancy. Risk of major congenital malformations (e.g., neural tube defects, orofacial clefts) in first trimester. Second and third trimester exposure associated with fetal growth restriction, oligohydramnios, neonatal renal dysfunction, and skull ossification defects. |
| Fetal Monitoring | Confirm negative pregnancy test before initiation. Monthly pregnancy testing during therapy. Ultrasound to assess fetal growth and amniotic fluid volume if exposure occurs. |
| Fertility Effects | Men: may cause reduced sperm count and motility; reversible upon discontinuation. Women: no direct effect on female fertility reported, but pregnancy contraindicated. |
| XTRELUS (lixivaptan) is a selective vasopressin V2 receptor antagonist indicated for the treatment of hyponatremia secondary to syndrome of inappropriate antidiuretic hormone (SIADH) in adults. Initiate therapy in a hospital setting to monitor serum sodium and volume status. Rapid correction of hyponatremia can cause osmotic demyelination syndrome; do not exceed a 6-8 mEq/L rise in 24 hours. Discontinue if serum sodium rises too quickly. Avoid use in patients with hypovolemic hyponatremia, anuria, or concurrent use of strong CYP3A4 inhibitors. Monitor for liver enzyme elevations; discontinue if clinically significant hepatotoxicity occurs. |
| Patient Advice | Take XTRELUS exactly as prescribed, typically once daily with or without food. · Do not drink large amounts of water while taking XTRELUS unless directed by your doctor, as it can cause excessive thirst and water intake may lead to electrolyte imbalance. · Avoid grapefruit and grapefruit juice as they can increase the level of XTRELUS in your blood and raise the risk of side effects. · Seek immediate medical attention if you experience signs of allergic reaction (rash, hives, difficulty breathing) or liver problems (yellowing of skin or eyes, dark urine, persistent nausea). · Your doctor will monitor your blood sodium levels and liver function regularly during treatment. · Do not stop taking XTRELUS without consulting your doctor, as abrupt discontinuation may cause a rapid increase in serum sodium. · Inform your doctor if you become pregnant or plan to breastfeed; XTRELUS is not recommended during pregnancy. |