ERTUGLIFLOZIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ERTUGLIFLOZIN (ERTUGLIFLOZIN).
Selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, reduces renal glucose reabsorption, increasing urinary glucose excretion.
| Metabolism | Primarily metabolized via glucuronidation by UGT1A9 and UGT2B7; minor CYP-mediated metabolism (CYP3A4, CYP1A2). |
| Excretion | Approximately 40-50% of the dose is excreted unchanged in the urine via glomerular filtration and active tubular secretion; about 50% is excreted in feces (mainly as unchanged drug and minor metabolites). |
| Half-life | Terminal elimination half-life is approximately 12-14 hours, supporting once-daily dosing. In renal impairment, half-life may be prolonged. |
| Protein binding | Approximately 95% bound to serum proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is approximately 100 L (about 1.4 L/kg), indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 100% (not affected by food). |
| Onset of Action | Glycosuria begins within 1-2 hours after oral administration; peak effect on urinary glucose excretion occurs at 3-6 hours. |
| Duration of Action | Duration of action is at least 24 hours, allowing once-daily dosing. The effect on urinary glucose excretion persists beyond 24 hours but diminishes over time. |
5 mg orally once daily, taken in the morning. May increase to 15 mg orally once daily if tolerated and additional glycemic control is needed.
| Dosage form | TABLET |
| Renal impairment | eGFR 30 to <60 mL/min/1.73 m²: 5 mg orally once daily; eGFR <30 mL/min/1.73 m²: not recommended; ESRD or on dialysis: contraindicated. |
| Liver impairment | Mild to moderate hepatic impairment (Child-Pugh A or B): no dose adjustment needed. Severe hepatic impairment (Child-Pugh C): not recommended due to lack of data. |
| Pediatric use | Not approved for use in pediatric patients; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment recommended solely based on age. Monitor renal function more frequently in elderly patients, particularly those with eGFR <60 mL/min/1.73 m², and adjust accordingly. Elderly patients may be at higher risk for volume depletion and hypotension. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ERTUGLIFLOZIN (ERTUGLIFLOZIN).
| Breastfeeding | No data on human milk excretion; M/P ratio unknown. Based on molecular weight and lack of human studies, a risk to the breastfed infant cannot be excluded. It is recommended to discontinue breastfeeding or avoid the drug during lactation. |
| Teratogenic Risk | ERTUGLIFLOZIN is contraindicated in the second and third trimesters due to potential fetal renal toxicity. First trimester exposure may be associated with a low risk of malformations; however, data are limited. Animal studies have shown fetal renal pelvis dilation and delayed ossification at high doses. |
■ FDA Black Box Warning
None.
| Serious Effects |
["History of serious hypersensitivity reaction to ertugliflozin","Severe renal impairment (eGFR <30 mL/min/1.73 m²), end-stage renal disease, or dialysis"]
| Precautions | ["Diabetic ketoacidosis (sometimes atypical, euglycemic)","Acute kidney injury and impairment in renal function","Urosepsis and pyelonephritis","Lower limb amputation (primarily toe)","Hypotension","Genital mycotic infections","Increased LDL-C"] |
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| Fetal Monitoring |
| Monitor maternal blood glucose, renal function (serum creatinine, eGFR), volume status, and ketones. Fetal surveillance includes ultrasound for renal abnormalities (e.g., hydronephrosis) and growth parameters during second and third trimesters if exposure occurs. |
| Fertility Effects | No significant adverse effects on fertility in animal studies. In humans, no specific data on fertility impairment; however, caution is warranted due to potential hormonal influences. |