EMPAGLIFLOZIN
Clinical safety rating: caution
Animal studies have proved adverse effects but may be safe for humans
Sodium-glucose cotransporter 2 (SGLT2) inhibitor; reduces renal glucose reabsorption, increasing urinary glucose excretion.
| Metabolism | Primarily metabolized via glucuronidation by UGT1A8, UGT2B7, and UGT1A9; minimal CYP450 involvement. |
| Excretion | Renal (54% as unchanged drug) and fecal (41% as unchanged drug or metabolites); biliary excretion is minimal. |
| Half-life | Terminal elimination half-life is approximately 12.4 hours (range 10-18 h) in patients with T2DM; supports once-daily dosing. |
| Protein binding | 86.2% bound, primarily to albumin. |
| Volume of Distribution | Vd/F is approximately 118 L (1.7 L/kg for a 70 kg individual), indicating extensive extravascular distribution. |
| Bioavailability | Oral bioavailability is approximately 78%; absorption is not significantly affected by food. |
| Onset of Action | Oral: Onset of glucose lowering occurs within 1-2 hours; maximal urinary glucose excretion within 3-4 hours. |
| Duration of Action | Duration of action is 24 hours, providing sustained SGLT2 inhibition for once-daily dosing. |
10 mg orally once daily, with or without food; may increase to 25 mg once daily if eGFR ≥60 mL/min/1.73 m² and additional glycemic control needed.
| Dosage form | TABLET |
| Renal impairment | eGFR ≥45 mL/min/1.73 m²: no dose adjustment; eGFR 30-44 mL/min/1.73 m²: not recommended for glycemic control but may be used for heart failure (10 mg once daily); eGFR <30 mL/min/1.73 m²: contraindicated for glycemic control; for heart failure, use 10 mg once daily if eGFR ≥20 mL/min/1.73 m²; avoid initiation if eGFR <20 mL/min/1.73 m². |
| Liver impairment | Child-Pugh Class A or B: no dose adjustment; Child-Pugh Class C: not recommended due to limited data. |
| Pediatric use | Not approved for patients <18 years of age; safety and efficacy not established. |
| Geriatric use | No dose adjustment required based on age alone; consider renal function (eGFR) as primary modifier; monitor for volume depletion and hypotension, especially in patients ≥75 years or those on diuretics. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Diuretics may enhance the potential for volume depletion Can cause genital mycotic infections and volume depletion.
| Breastfeeding | M/P ratio unknown. Empagliflozin is excreted into rat milk; no human data available. Breastfeeding is not recommended during therapy due to potential for adverse effects on neonatal renal function and lack of safety data. |
| Teratogenic Risk | Empagliflozin is contraindicated in the second and third trimesters due to potential fetal renal toxicity. Animal studies have shown renal pelvic dilatation and delayed ossification at exposures similar to human therapeutic doses. In the first trimester, limited human data preclude definitive risk assessment, but drug should be avoided given availability of safer alternatives. |
■ FDA Black Box Warning
None
| Common Effects | heart failure |
| Serious Effects |
["History of serious hypersensitivity reaction to empagliflozin","Severe renal impairment (eGFR <30 mL/min/1.73 m²) or dialysis"]
| Precautions | ["Hypotension","Ketoacidosis","Acute kidney injury","Urosepsis and pyelonephritis","Hypoglycemia with insulin or sulfonylureas","Necrotizing fasciitis of perineum (Fournier gangrene)"] |
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| Fetal Monitoring | Maternal: renal function (serum creatinine, eGFR), electrolytes, volume status, and blood glucose. Fetal: ultrasound monitoring for renal anomalies if inadvertently exposed in second/third trimester. Assess neonatal renal function and blood glucose post-delivery if exposure occurred near term. |
| Fertility Effects | No human data on fertility. Animal studies show no adverse effects on fertility at doses up to 10 times the human clinical exposure. Male and female fertility not impaired in animal models. |