XTRELUS

Clinical safety rating: caution

Comprehensive clinical and safety monograph for XTRELUS (XTRELUS).

How it works

Selective inhibitor of the sodium-glucose cotransporter 2 (SGLT2) in the proximal renal tubules, reducing glucose reabsorption and lowering blood glucose levels.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for XTRELUS (XTRELUS).

Breastfeeding	No data available. Manufacturer advises discontinue breastfeeding or drug due to potential serious adverse reactions in nursing infant. M/P ratio unknown.
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

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Serious Effects

Absolute Contraindications

["History of serious hypersensitivity reaction to Xtrelus","Severe renal impairment (eGFR <30 mL/min/1.73 m2)","End-stage renal disease or dialysis","Patients with type 1 diabetes mellitus"]

Clinical Precautions

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"]

Clinical Tips & Counseling

Drug interactions

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XTRELUS

Clinical safety rating: caution

Comprehensive clinical and safety monograph for XTRELUS (XTRELUS).

How it works

Selective inhibitor of the sodium-glucose cotransporter 2 (SGLT2) in the proximal renal tubules, reducing glucose reabsorption and lowering blood glucose levels.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for XTRELUS (XTRELUS).

Breastfeeding	No data available. Manufacturer advises discontinue breastfeeding or drug due to potential serious adverse reactions in nursing infant. M/P ratio unknown.
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

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Serious Effects

Absolute Contraindications

["History of serious hypersensitivity reaction to Xtrelus","Severe renal impairment (eGFR <30 mL/min/1.73 m2)","End-stage renal disease or dialysis","Patients with type 1 diabetes mellitus"]