Dosing & Uses
Dosage Forms & Strengths
tablet
- 10mg
- 25mg
Type 2 Diabetes Mellitus
Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes
Also indicated to reduce the risk of cardiovascular death in adults with type 2 diabetes mellitus and cardiovascular disease
10 mg PO qDay
May increase to 25 mg/day if needed and tolerated
Dosage Modifications
Hepatic impairment: No dosage adjustment required
Renal Impairment
- eGFR ≥45 mL/min/1.73 m2: No dosage adjustment required
- eGFR 30-45 mL/min/1.73 m2: Do not initiate therapy; if already on it, discontinue therapy when eGFR persistently <45 mL/min/1.73 m2
- eGFR <30 mL/min/1.73 m2: Contraindicated
Dosing Considerations
Limitation of use: Not indicated for treatment of type 1 diabetes or diabetic ketoacidosis
Assess renal function before initiating and periodically thereafter
In patients with volume depletion, correcting this condition before initiating treatment
<18 years: Safety and efficacy not established
No dosage change is recommended based on age; see Adult Dosing
Risk of volume depletion-related adverse reactions increased in patients who were ≥75 yr to 2.1%, 2.3%, and 4.4% for placebo, 10 mg, and 25 mg, respectively
Risk of urinary tract infections increased in patients who were ≥75 yr to 10.5%, 15.7%, and 15.1% in patients randomized to placebo, 10 mg, and 25 mg, respectively
Interactions
Interaction Checker
No Results

Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor

Adverse Effects
1-10%
Urinary tract infection (7.6-9.3%)
Female genital mycotic infections (5.4-6.4%)
Upper respiratory tract infection (3.1-4%)
Increased urination (3.2-3.4%)
Dyslipidemia (2.9-3.9%)
Male genital mycotic infections (1.6-3.1%)
Arthralgia (2.3-2.4%)
Nausea (1.1-2.3%)
Polydipsia (1.5-1.7%)
<1%
Adverse reactions related to volume depletion (eg, blood pressure [ambulatory] decreased, blood pressure systolic decreased, dehydration, hypotension, hypovolemia, orthostatic hypotension, and syncope)
Increased urination (eg, nocturia)
Postmarketing reports
Ketoacidosis
Urosepsis and pyelonephritis
Necrotizing fasciitis of the perineum (Fournier’s gangrene)
Angioedema
Skin reactions
Warnings
Contraindications
Serious hypersensitivity to empagliflozin (eg, anaphylaxis, angioedema)
Severe renal impairment (eGFR <30 mL/min/1.73 m2), end-stage renal disease, or patients on dialysis
Cautions
Causes intravascular volume contraction; symptomatic hypotension may occur after initiating, particularly in patients with renal impairment, low systolic blood pressure, on diuretics, or in the elderly
Increases serum creatinine and decreases eGFR; risk increased in elderly or those with moderate renal impairment
Increased incidence of bone fractures reported; American Diabetes Association recommends avoiding sodium glucose cotransporter-2 inhibitors in patients with fracture risk factors
Genital mycotic infections may occur; patients with history of genital mycotic infections and uncircumcised males are more susceptible
Increases risk of urinary tract infections (UTIs), including life-threatening urosepsis and pyelonephritis that started as UTIs
Dose-related increases in LDL-C reported
No conclusive evidence of macrovascular risk reduction with empagliflozin or any other antidiabetic agent
Serious hypersensitivity reactions (eg, angioedema) reported; if a hypersensitivity reaction occurs, discontinue treatment; treat promptly per standard of care, and monitor until signs and symptoms resolve
Renal function
- Acute kidney injury reported
- Consider risk factors, including hypovolemia, heart failure, and chronic renal insufficiency or use of medications, including diuretics, ACE inhibitors, NSAIDs, or angiotensin receptor blockers
- Correct volume status before initiating if needed and monitor renal function periodically thereafter
Necrotizing fasciitis
- Necrotizing fasciitis of the perineum (Fournier gangrene) reported with SGLT2 inhibitors
- Signs and symptoms include tenderness, redness, or swelling of the genitals or the area from the genitals back to the rectum, and have a fever above 100.4ºF or a general feeling of being unwell
- If suspected, discontinue SGLT2 inhibitor and start treatment immediately with broad-spectrum antibiotics and surgical debridement if necessary
Ketoacidosis
- Before initiating therapy, consider factors in patient history that may predispose to ketoacidosis, including pancreatic insulin deficiency from any cause, caloric restriction, and alcohol abuse
- Consider temporarily discontinuing therapy for at least 3 days for patients who undergo scheduled surgery
- Consider monitoring for ketoacidosis and temporarily discontinuing therapy in other clinical situations known to predispose to ketoacidosis (eg, prolonged fasting due to acute illness or post-surgery); ensure risk factors for ketoacidosis are resolved prior to restarting therapy
- Restart once the patient’s oral intake is back to baseline and any other risk factors for ketoacidosis (blood acid buildup) are resolved
Drug interactions overview
- Hypoglycemia risk increased with insulin and insulin secretagogues (eg, sulfonylureas); a lower dose of insulin or insulin secretagogue may be required
Laboratory testing
- Urine glucose tests is not recommended in patients taking SGLT2 inhibitors, as SGLT2 inhibitors, increase urinary glucose excretion and lead to positive urine glucose tests; use alternative methods to monitor glycemic control
- 1,5-AG assay is not recommended, as measurements of 1,5-AG are unreliable in assessing glycemic control in patients taking SGLT2 inhibitors; use alternative methods to monitor glycemic control
Pregnancy & Lactation
Pregnancy
Based on animal data showing adverse renal effects, use not recommended during the second and third trimesters of pregnancy
Limited data available in pregnant women are insufficient to determine a drug-associated risk for major birth defects and miscarriage
There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy
Animal data
- In animal studies, adverse renal changes were observed in rats when empagliflozin was administered during period of renal development corresponding to the late second and third trimesters of human pregnancy
- Doses ~13-times the maximum clinical dose caused renal pelvic and tubule dilatations were reversible
- Not teratogenic in rats and rabbits up to 300 mg/kg/day, which approximates 48-times and 128-times, respectively, the maximum clinical dose of 25 mg when administered during organogenesis
Clinical considerations
- Poorly controlled diabetes in pregnancy increases maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, stillbirth, and delivery complications; poorly controlled diabetes increases fetal risk for major birth defects, still birth, and macrosomia related morbidity
Lactation
There is no information regarding presence in human milk, the effects on breastfed infant or on milk production
Empagliflozin is present in the milk of lactating rats
Because of potential for serious adverse reactions in a breastfed infant, advise women that it is not recommended while breastfeeding
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Selective sodium-glucose transporter-2 (SGLT2) inhibitor
SGLT2 is expressed in the proximal renal tubules and is responsible for the majority of the reabsorption of filtered glucose from the tubular lumen; SGLT2 inhibitors reduce glucose reabsorption and lower the renal threshold for glucose, thereby increasing urinary glucose excretion
Absorption
Peak plasma time: 1.5 hr
Peak plasma concentration: 259 nmol/L (10 mg/day); 687 nmol/L (25 mg/day)
AUC: 1870 nmol•hr/L (10 mg/day); 4740 nmol•hr/L (25 mg/day)
Distribution
Protein bound: 86.2%
Red blood cell partitioning: 36.8%
Vd: 73.8 L
Metabolism
Primary route of metabolism is glucuronidation by the uridine 5'-diphospho-glucuronosyltransferases UGT2B7, UGT1A3, UGT1A8, and UGT1A9
No major metabolites were detected and the most abundant metabolites were 3 glucuronide conjugates (2-O-, 3-O-, and 6-O-glucuronide)
Systemic exposure of each metabolite was <10%
Elimination
Half-life: 12.4 hr
Clearance: 10.6 L/hr
Excretion: 54.4% urine; 41.2% feces
Administration
Oral Administration
May take with or without food
Advise patient to have adequate fluid intake to decreased risk of hypotension
Storage
Store at 25ºC (77ºF); excursions permitted to 15-30ºC (59-86ºF)
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