Data from Clinical Trials

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS: Hypersensitivity to empagliflozin or any of the excipients in JARDIANCE, reactions such as angioedema have occurred.

WARNINGS AND PRECAUTIONS

Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis: JARDIANCE increases the risk of life-threatening ketoacidosis in patients with type 1 diabetes and fatal ketoacidosis has occurred with JARDIANCE. Type 2 diabetes and pancreatic disorders are also risk factors for ketoacidosis and fatal events of ketoacidosis have been reported in patients with type 2 diabetes using JARDIANCE. Precipitating conditions for diabetic ketoacidosis or other ketoacidosis include under-insulinization due to insulin dose reduction or missed insulin doses, acute febrile illness, reduced caloric intake, ketogenic diet, surgery, volume depletion, and alcohol abuse. Signs and symptoms of diabetic ketoacidosis are consistent with dehydration and severe metabolic acidosis and include nausea, vomiting, abdominal pain, generalized malaise, and shortness of breath. Assess patients who present with signs and symptoms of metabolic ketoacidosis, regardless of blood glucose levels. If suspected, discontinue JARDIANCE, treat promptly and monitor for resolution before restarting. Consider ketone monitoring in patients with type 1 diabetes mellitus as well as in others at risk for ketoacidosis. Withhold JARDIANCE in clinical situations known to predispose to ketoacidosis and resume when clinically stable. Educate all patients on the signs and symptoms of ketoacidosis and instruct patients to discontinue JARDIANCE and seek medical attention immediately if signs and symptoms occur.

Volume Depletion: JARDIANCE can cause intravascular volume depletion which may manifest as symptomatic hypotension or acute transient changes in creatinine. Acute kidney injury requiring hospitalization and dialysis has been reported in patients with type 2 diabetes receiving SGLT2 inhibitors, including JARDIANCE. Before initiating, assess volume status and renal function in patients with impaired renal function (eGFR <60 mL/min/1.73 m2), elderly patients or patients on loop diuretics. In patients with volume depletion, correct this condition before initiating JARDIANCE. After initiating, monitor for signs and symptoms of volume depletion and renal function.

Urosepsis and Pyelonephritis: Serious urinary tract infections including urosepsis and pyelonephritis requiring hospitalization have been identified in patients receiving JARDIANCE. Treatment with JARDIANCE increases the risk for urinary tract infections. Evaluate for signs and symptoms of urinary tract infections and treat promptly.

Hypoglycemia: In adult patients, the use of JARDIANCE in combination with insulin or insulin secretagogues can increase the risk of hypoglycemia. In pediatric patients aged 10 years and older, the risk of hypoglycemia was higher with JARDIANCE regardless of insulin use. The risk of hypoglycemia may be lowered by a reduction in the dose of sulfonylurea (or other concomitantly administered insulin secretagogues) or insulin.

Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene): Serious, life-threatening cases requiring urgent surgical intervention have occurred in both females and males receiving JARDIANCE. Serious outcomes have included hospitalization, multiple surgeries and death. Assess patients presenting with pain or tenderness, erythema, or swelling in the genital or perineal area, along with fever or malaise. If suspected, institute prompt treatment and discontinue JARDIANCE.

Genital Mycotic Infections: JARDIANCE increases the risk for genital mycotic infections, especially in patients with prior infections. Monitor and treat as appropriate.

Lower Limb Amputation: Lower limb amputations have been observed in patients with chronic kidney disease taking JARDIANCE. Peripheral artery disease, and diabetic foot infection (including osteomyelitis), were the most common precipitating medical events leading to the need for an amputation. The risk of amputation was highest in patients with a baseline history of diabetic foot, peripheral artery disease (including previous amputation) or diabetes. Counsel patients receiving JARDIANCE about the importance of routine preventative foot care and monitor for signs and symptoms of diabetic foot infection (including osteomyelitis), new pain or tenderness, sores or ulcers involving the lower limbs, and institute appropriate treatment.

Hypersensitivity Reactions: Serious hypersensitivity reactions have occurred with JARDIANCE (angioedema). If hypersensitivity reactions occur, discontinue JARDIANCE, treat promptly, and monitor until signs and symptoms resolve.

MOST COMMON ADVERSE REACTIONS (≥5%): Urinary tract infections and female genital mycotic infections.

DRUG INTERACTIONS:

Diuretics: Coadministration with diuretics may enhance the potential for volume depletion. Monitor for signs and symptoms.

Lithium: Concomitant use with lithium may decrease serum lithium concentrations. Monitor more frequently during JARDIANCE initiation and dosage changes.

USE IN SPECIAL POPULATIONS

Pregnancy: JARDIANCE is not recommended during the second and third trimesters.

Lactation: JARDIANCE is not recommended while breastfeeding.

Geriatric Use: JARDIANCE is expected to have diminished glycemic efficacy in elderly patients with renal impairment. Assess renal function more frequently in elderly patients. The incidence of volume depletion-related adverse reactions and urinary tract infections increased in T2D patients ≥75 years treated with empagliflozin.

INDICATIONS AND LIMITATIONS OF USE

EMPA-REG OUTCOME trial design: A randomized, double-blind, parallel-group trial comparing the risk of experiencing a major adverse CV event between JARDIANCE and placebo when these were added to and used concomitantly with standard-of-care treatments for T2D and CVD. A total of 7020 patients were treated (JARDIANCE 10 mg [n=2345]; JARDIANCE 25 mg [n=2342]; placebo [n=2333]) and followed for a median of 3.1 years. All patients had established CVD at baseline, including one or more of the following: a documented history of CAD, PAD, MI, or stroke. The primary outcome was reduction in risk of CV events, defined by the composite of CV death, nonfatal MI, or nonfatal stroke.1,5

EMPEROR-Reduced and EMPEROR-Preserved trial design: EMPEROR-Reduced was a randomized, double-blind, placebo-controlled study conducted in patients with chronic HF (NYHA functional class II-IV) with reduced EF (LVEF 40% or less) to evaluate the efficacy and safety of JARDIANCE 10 mg once daily, as adjunct to standard of care therapy. The primary endpoint was the time to first event of either CV death or hHF. Occurrence of hHF (first and recurrent) was assessed as a key secondary endpoint. EMPEROR-Preserved followed the same design in patients with chronic HF patients with preserved EF (LVEF >40%).

EMPA-KIDNEY trial design: A randomized, parallel-group, double-blind, placebo-controlled study of 6609 adult patients with CKD (eGFR ≥20 to <45 mL/min/1.73 m2; or eGFR ≥45 to <90 mL/min/1.73 m2 with uACR ≥200 mg/g), evaluating the efficacy and safety of JARDIANCE 10 mg (n=3304) vs placebo (n=3305) as adjunct to standard of care therapy. The primary endpoint was a composite of: sustained decrease in eGFR of ≥40% from baseline, sustained decrease in eGFR to <10 mL/min/1.73 m2, ESKD (the initiation of maintenance dialysis or receipt of a kidney transplant), or CV or renal death.

3P-MACE=3-point major adverse cardiovascular event; ARR=absolute risk reduction; CAD=coronary artery disease; CI=confidence interval; CKD=chronic kidney disease; CV=cardiovascular; CVD=cardiovascular disease; eGFR=estimated glomerular filtration rate; eCVD=estimated cardiovascular disease; EF=ejection fraction; ESKD=end-stage kidney disease; HF=heart failure; HFpEF=heart failure with preserved ejection fraction; HFrEF=heart failure with reduced ejection fraction; hHF=hospitalization for heart failure; HR=hazard ratio; IV=intravenous; LVEF=left ventricular ejection fraction; MI=myocardial infarction; NBRx=new-to-brand prescription; NNT=number needed to treat; NYHA=New York Heart Association; PAD=peripheral artery disease; RAASi=renin-angiotensin-aldosterone system inhibitor; RRR=relative risk reduction; SOC=standard of care; SGLT2i=sodium-glucose cotransporter-2 inhibitor; T1D=type 1 diabetes; T2D=type 2 diabetes; TRx=total prescriptions; uACR=urine albumin-to-creatinine ratio.