Get your patient on Jardiance (Empagliflozin)

JARDIANCE is indicated:

• to reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure.
• to reduce the risk of sustained decline in eGFR, end-stage kidney disease, cardiovascular death, and hospitalization in adults with chronic kidney disease at risk of progression.
• to reduce the risk of cardiovascular death in adults with type 2 diabetes mellitus and established cardiovascular disease.
• as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients aged 10 years and older with type 2 diabetes mellitus.

• Assess renal function before initiating and as clinically indicated. Assess volume status and correct volume depletion before initiating. (
  2.1 Testing Prior to Initiation of JARDIANCE

  • Assess renal function before initiating JARDIANCE and as clinically indicated
    [seeWarnings and Precautions (5.2)]
    .
    • Use for glycemic control is not recommended in patients with an eGFR less than 30 mL/min/1.73 m²
      [seeUse in Specific Populations (8.6)].
  • Assess volume status. In patients with volume depletion, correct this condition before initiating JARDIANCE
    [seeWarnings and Precautions (5.2)andUse in Specific Populations (8.5,8.6)].
  )
• Recommended dosage is 10 mg orally once daily in the morning, taken with or without food. (
  2.2 Recommended Dosage

  Table 1 presents the recommended dosage of JARDIANCE in adult and pediatric patients aged 10 years and older.

  Table 1 Recommended Dosage of JARDIANCE

  Population	Indication	Recommended Dosage
  Adults	Reduce the risk of cardiovascular death and hospitalization in patients with heart failure	10 mg orally once daily in the morning, taken with or without food.
  	Reduce the risk of sustained decline in eGFR, end-stage kidney disease, cardiovascular death, and hospitalization in adults with chronic kidney disease at risk of progression.
  	Reduce the risk of cardiovascular death in patients with type 2 diabetes mellitus with established cardiovascular disease
  	Glycemic control in type 2 diabetes mellitus	10 mg orally once daily in the morning, taken with or without food. For additional glycemic control, may increase to 25 mg orally once daily in patients tolerating 10 mg once daily.
  Pediatric patients aged 10 years and older	Glycemic control in type 2 diabetes mellitus	10 mg orally once daily in the morning, taken with or without food. For additional glycemic control, may increase to 25 mg orally once daily in patients tolerating 10 mg once daily.
  )
• For additional glycemic control, dosage may be increased to 25 mg orally once daily in patients tolerating JARDIANCE. (
  2.2 Recommended Dosage

  Table 1 presents the recommended dosage of JARDIANCE in adult and pediatric patients aged 10 years and older.

  Table 1 Recommended Dosage of JARDIANCE

  Population	Indication	Recommended Dosage
  Adults	Reduce the risk of cardiovascular death and hospitalization in patients with heart failure	10 mg orally once daily in the morning, taken with or without food.
  	Reduce the risk of sustained decline in eGFR, end-stage kidney disease, cardiovascular death, and hospitalization in adults with chronic kidney disease at risk of progression.
  	Reduce the risk of cardiovascular death in patients with type 2 diabetes mellitus with established cardiovascular disease
  	Glycemic control in type 2 diabetes mellitus	10 mg orally once daily in the morning, taken with or without food. For additional glycemic control, may increase to 25 mg orally once daily in patients tolerating 10 mg once daily.
  Pediatric patients aged 10 years and older	Glycemic control in type 2 diabetes mellitus	10 mg orally once daily in the morning, taken with or without food. For additional glycemic control, may increase to 25 mg orally once daily in patients tolerating 10 mg once daily.
  )
• Withhold JARDIANCE for at least 3 days, if possible, prior to surgery or procedures associated with prolonged fasting. (
  2.3 Temporary Interruption for Surgery

  Withhold JARDIANCE for at least 3 days, if possible, prior to surgery or procedures associated with prolonged fasting. Resume JARDIANCE when the patient is clinically stable and has resumed oral intake

  [seeWarnings and Precautions (5.1)andClinical Pharmacology (12.2)].
  )

JARDIANCE tablets available as:

• 10 mg pale yellow, round, biconvex and bevel-edged, film-coated tablets debossed with "S 10" on one side and the Boehringer Ingelheim company symbol on the other side.
• 25 mg pale yellow, oval, biconvex, film-coated tablets debossed with "S 25" on one side and the Boehringer Ingelheim company symbol on the other side.

• Pregnancy:
  Advise females of the potential risk to a fetus especially during the second and third trimesters. (
  8.1 Pregnancy

  Risk Summary

  Based on animal data showing adverse renal effects, JARDIANCE is not recommended during the second and third trimesters of pregnancy.

  The limited available data with JARDIANCE in pregnant women are not sufficient 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

  [seeClinical Considerations]

  .

  In animal studies, adverse renal changes were observed in rats when empagliflozin was administered during a period of renal development corresponding to the late second and third trimesters of human pregnancy. Doses approximately 13-times the maximum clinical dose caused renal pelvic and tubule dilatations that were reversible

  [seeData]

  .

  The estimated background risk of major birth defects is 6% to 10% in women with pre-gestational diabetes with a HbA1c >7 and has been reported to be as high as 20% to 25% in women with HbA1c >10. The estimated background risk of miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

  Clinical Considerations

  Disease-associated maternal and/or embryo/fetal risk

  Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity.

  Data

  Animal Data

  Empagliflozin dosed directly to juvenile rats from postnatal day (PND) 21 until PND 90 at doses of 1, 10, 30, and 100 mg/kg/day caused increased kidney weights and renal tubular and pelvic dilatation at 100 mg/kg/day, which approximates 13-times the maximum clinical dose of 25 mg, based on AUC. These findings were not observed after a 13-week, drug-free recovery period. These outcomes occurred with drug exposure during periods of renal development in rats that correspond to the late second and third trimester of human renal development.

  In embryo-fetal development studies in rats and rabbits, empagliflozin was administered for intervals coinciding with the first trimester period of organogenesis in humans. Doses up to 300 mg/kg/day, which approximates 48-times (rats) and 128-times (rabbits) the maximum clinical dose of 25 mg (based on AUC), did not result in adverse developmental effects. In rats, at higher doses of empagliflozin causing maternal toxicity, malformations of limb bones increased in fetuses at 700 mg/kg/day or 154-times the 25 mg maximum clinical dose. Empagliflozin crosses the placenta and reaches fetal tissues in rats. In the rabbit, higher doses of empagliflozin resulted in maternal and fetal toxicity at 700 mg/kg/day, or 139-times the 25 mg maximum clinical dose.

  In pre- and postnatal development studies in pregnant rats, empagliflozin was administered from gestation day 6 through to lactation day 20 (weaning) at up to 100 mg/kg/day (approximately 16-times the 25 mg maximum clinical dose) without maternal toxicity. Reduced body weight was observed in the offspring at greater than or equal to 30 mg/kg/day (approximately 4-times the 25 mg maximum clinical dose).
  )
• Lactation:
  Not recommended when breastfeeding. (
  8.2 Lactation

  Risk Summary

  There is limited information regarding the presence of JARDIANCE in human milk, the effects of JARDIANCE on the breastfed infant or the effects on milk production. Empagliflozin is present in the milk of lactating rats

  [seeData]

  . Since human kidney maturation occurs

  in utero

  and during the first 2 years of life when lactational exposure may occur, there may be risk to the developing human kidney.

  Because of the potential for serious adverse reactions in a breastfed infant, including the potential for empagliflozin to affect postnatal renal development, advise patients that use of JARDIANCE is not recommended while breastfeeding.

  Data

  Empagliflozin was present at a low level in rat fetal tissues after a single oral dose to the dams at gestation day 18. In rat milk, the mean milk to plasma ratio ranged from 0.634 to 5, and was greater than one from 2 to 24 hours post-dose. The mean maximal milk to plasma ratio of 5 occurred at 8 hours post-dose, suggesting accumulation of empagliflozin in the milk. Juvenile rats directly exposed to empagliflozin showed a risk to the developing kidney (renal pelvic and tubular dilatations) during maturation.
  )
• Geriatric Patients:
  Higher incidence of adverse reactions related to volume depletion and reduced renal function. (
  8.5 Geriatric Use

  In glycemic control trials in patients with type 2 diabetes mellitus, a total of 2,721 (32%) patients treated with JARDIANCE were 65 years of age and older, and 491 (6%) were 75 years of age and older. JARDIANCE is expected to have diminished glycemic efficacy in elderly patients with renal impairment

  [seeUse in Specific Populations (8.6)]

  . The risk of volume depletion-related adverse reactions increased in patients who were 75 years of age and older to 2.1%, 2.3%, and 4.4% for placebo, JARDIANCE 10 mg, and JARDIANCE 25 mg. The risk of urinary tract infections increased in patients who were 75 years of age and older to 10.5%, 15.7%, and 15.1% in patients randomized to placebo, JARDIANCE 10 mg, and JARDIANCE 25 mg, respectively

  [seeWarnings and Precautions (5.2)andAdverse Reactions (6.1)]

  .

  In the EMPEROR-Reduced, EMPEROR-Preserved, and EMPA-KIDNEY trials, no overall differences in safety and effectiveness have been observed between patients 65 years of age and older and younger adult patients. EMPEROR-Reduced included 1,188 (64%) patients treated with JARDIANCE 65 years of age and older, and 503 (27%) patients 75 years of age and older. EMPEROR-Preserved included 2,403 (80%) patients treated with JARDIANCE 65 years of age and older, and 1,281 (43%) patients 75 years of age and older. EMPA-KIDNEY included 1,803 (55%) patients treated with JARDIANCE 65 years of age and older, and 758 (23%) patients 75 years of age and older.
  )
• Renal Impairment:
  Higher incidence of adverse reactions related to reduced renal function. (
  8.6 Renal Impairment

  The efficacy and safety of JARDIANCE for glycemic control were evaluated in a trial of adult patients with type 2 diabetes mellitus with mild and moderate renal impairment (eGFR 30 to less than 90 mL/min/1.73 m²)

  [seeClinical Studies (14.1)]

  . In this trial, 195 adult patients exposed to JARDIANCE had an eGFR between 60 and 90 mL/min/1.73 m², 91 adult patients exposed to JARDIANCE had an eGFR between 45 and 60 mL/min/1.73 m², and 97 patients exposed to JARDIANCE had an eGFR between 30 and 45 mL/min/1.73 m². The glucose lowering benefit of JARDIANCE 25 mg decreased in adult patients with worsening renal function. The risks of renal impairment, volume depletion adverse reactions and urinary tract infection-related adverse reactions increased with worsening renal function

  [seeWarnings and Precautions (5.2)]

  . Use of JARDIANCE for glycemic control in patients without established cardiovascular disease or cardiovascular risk factors is not recommended when eGFR is less than 30 mL/min/1.73 m².

  JARDIANCE was evaluated in 7,020 adult patients with type 2 diabetes and established cardiovascular disease (eGFR greater than or equal to 30 mL/min/1.73 m²) in the EMPA-REG OUTCOME trial, in a total of 9,718 patients with heart failure (eGFR greater than or equal to 20 mL/min/1.73 m²) in the EMPEROR-Reduced and EMPEROR-Preserved trials, and in 6,609 adult patients with chronic kidney disease (eGFR 20 to 90 mL/min/1.73 m²) in the EMPA-KIDNEY study. The safety profile across eGFR subgroups in these trials was consistent with the known safety profile

  [seeAdverse Reactions (6.1)andClinical Studies (14.3,14.4,14.5)].

  Efficacy and safety trials with JARDIANCE did not enroll adult patients with an eGFR less than 20 mL/min/1.73 m²or on dialysis. Once enrolled, adult patients in the EMPA-REG OUTCOME, EMPEROR-Reduced, EMPEROR-Preserved, and EMPA-KIDNEY trials were not required to discontinue therapy for worsening of eGFR to less than 20 mL/min/1.73 m²or initiation of dialysis

  [seeClinical Studies (14.3,14.4,14.5)].
  )

JARDIANCE is contraindicated in patients:

• with a hypersensitivity to empagliflozin or any of the excipients in JARDIANCE, reactions such as angioedema have occurred
  [see

  5.6 Hypersensitivity Reactions

  There have been postmarketing reports of serious hypersensitivity reactions (e.g., angioedema) in patients treated with JARDIANCE. If a hypersensitivity reaction occurs, discontinue JARDIANCE; treat promptly per standard of care, and monitor until signs and symptoms resolve. JARDIANCE is contraindicated in patients with hypersensitivity to empagliflozin or any of the excipients in JARDIANCE

  [seeContraindications (4)]

  .

  ]
  .

• Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis:
  Consider ketone monitoring in patients with type 1 diabetes mellitus and consider ketone monitoring in others at risk for ketoacidosis, as indicated. Assess for ketoacidosis regardless of presenting blood glucose levels and discontinue JARDIANCE if ketoacidosis is suspected. Monitor patients for resolution of ketoacidosis before restarting. (
  5.1 Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis

  In patients with type 1 diabetes mellitus, JARDIANCE significantly increases the risk of diabetic ketoacidosis, a life-threatening event, beyond the background rate. In placebo-controlled trials of patients with type 1 diabetes mellitus, the risk of ketoacidosis was markedly increased in patients who received sodium glucose co-transporter 2 (SGLT2) inhibitors compared to patients who received placebo and fatal ketoacidosis has occurred with JARDIANCE. JARDIANCE is not indicated for glycemic control in patients with type 1 diabetes mellitus.

  Type 2 diabetes mellitus and pancreatic disorders (e.g., history of pancreatitis or pancreatic surgery) are also risk factors for ketoacidosis. There have been postmarketing reports of fatal events of ketoacidosis in patients with type 2 diabetes mellitus using SGLT2 inhibitors, including 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 are consistent with dehydration and severe metabolic acidosis and include nausea, vomiting, abdominal pain, generalized malaise, and shortness of breath. Blood glucose levels at presentation may be below those typically expected for diabetic ketoacidosis (e.g., less than 250 mg/dL). Ketoacidosis and glucosuria may persist longer than typically expected. Urinary glucose excretion persists for 3 days after discontinuing JARDIANCE

  [seeClinical Pharmacology (12.2)]

  ; however, there have been postmarketing reports of ketoacidosis and/or glucosuria lasting greater than 6 days and some up to 2 weeks after discontinuation of SGLT2 inhibitors.

  Consider ketone monitoring in patients with type 1 diabetes mellitus and consider ketone monitoring in others at risk for ketoacidosis if indicated by the clinical situation. Assess for ketoacidosis regardless of presenting blood glucose levels in patients who present with signs and symptoms consistent with severe metabolic acidosis. If ketoacidosis is suspected, discontinue JARDIANCE, promptly evaluate, and treat ketoacidosis, if confirmed. Monitor patients for resolution of ketoacidosis before restarting JARDIANCE.

  Withhold JARDIANCE, if possible, in temporary clinical situations that could predispose patients to ketoacidosis. Resume JARDIANCE when the patient is clinically stable and has resumed oral intake

  [seeDosage and Administration (2.3)]

  .

  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:
  Before initiating JARDIANCE, assess volume status and renal function in patients with impaired renal function, elderly patients, or patients on loop diuretics. Monitor for signs and symptoms during therapy. (
  5.2 Volume Depletion

  JARDIANCE can cause intravascular volume depletion which may sometimes manifest as symptomatic hypotension or acute transient changes in creatinine

  [seeAdverse Reactions (6.1)]

  . There have been post-marketing reports of acute kidney injury, some requiring hospitalization and dialysis, in patients with type 2 diabetes mellitus receiving SGLT2 inhibitors, including JARDIANCE. Patients with impaired renal function (eGFR less than 60 mL/min/1.73 m²), elderly patients, or patients on loop diuretics may be at increased risk for volume depletion or hypotension. Before initiating JARDIANCE in patients with one or more of these characteristics, assess volume status and renal function. In patients with volume depletion, correct this condition before initiating JARDIANCE. Monitor for signs and symptoms of volume depletion, and renal function after initiating therapy.
  )
• Genitourinary Infections, including Urosepsis, Pyelonephritis, Necrotizing Fasciitis of the Perineum (Fournier's Gangrene), and Genital Mycotic Infections:
  Monitor patients for signs and symptoms of genitourinary infections and treat promptly, if indicated. Immediately evaluate patients presenting with pain or tenderness, erythema, or swelling in the genital or perineal area, along with fever or malaise, for necrotizing fasciitis and if suspected, discontinue JARDIANCE, and promptly institute appropriate medical and/or surgical intervention. (
  5.3 Genitourinary Infections, including Urosepsis, Pyelonephritis, Necrotizing Fasciitis of the Perineum (Fournier's Gangrene), and Genital Mycotic Infections

  JARDIANCE increases urinary glucose excretion

  [seeClinical Pharmacology (12.2)]

  and increases the risk of genitourinary infections including urinary tract infections and genital mycotic infections in both male and female patients

  [seeAdverse Reactions (6.1)]

  .

  Serious genitourinary infections, including urosepsis, pyelonephritis, and necrotizing fasciitis of the perineum (Fournier's gangrene, a rare life-threatening infection requiring urgent surgical intervention), have occurred in patients with and without diabetes mellitus receiving SGLT2 inhibitors, including JARDIANCE

  [seeAdverse Reactions (6.2)].

  Cases have required hospitalization. In patients with Fournier's gangrene, serious outcomes have included multiple surgeries and death.

  Patients with a history of chronic or recurrent genitourinary infections are more likely to develop genitourinary infections when using JARDIANCE. Monitor patients for signs and symptoms of genitourinary infections and treat promptly, if indicated.

  Immediately evaluate patients presenting with pain or tenderness, erythema, or swelling in the genital or perineal area, along with fever or malaise, for necrotizing fasciitis. If suspected, discontinue JARDIANCE and promptly institute appropriate medical and/or surgical intervention.
  )
• Hypoglycemia:
  Adult patients taking an insulin secretagogue or insulin may have an increased risk of hypoglycemia. In pediatric patients 10 years of age and older, the risk of hypoglycemia was higher regardless of insulin use. Consider lowering the dosage of insulin secretagogue or insulin to reduce the risk of hypoglycemia when initiating JARDIANCE. (
  5.4 Hypoglycemia

  Insulin and insulin secretagogues are known to cause hypoglycemia. In adult patients, the risk of hypoglycemia may be increased when JARDIANCE is used in combination with insulin secretagogues (e.g., sulfonylurea) or insulin. In pediatric patients aged 10 years and older, the risk of hypoglycemia was higher with JARDIANCE regardless of insulin use

  [seeAdverse Reactions (6.1)]

  .

  The risk of hypoglycemia may be lowered by a reduction in the dose of sulfonylurea (or other concomitantly administered insulin secretagogues) or insulin. Inform patients using these concomitant medications and pediatric patients of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia.
  )
• Lower Limb Amputation:
  Monitor patients for infections or ulcers of lower limbs, and institute appropriate treatment (
  5.5 Lower Limb Amputation

  In some clinical studies with SGLT2 inhibitors an imbalance in the incidence of lower limb amputation has been observed. Across four JARDIANCE outcome trials, lower limb amputation event rates were 4.3 and 5.0 events per 1,000 patient-years in the placebo group and the JARDIANCE 10 mg or 25 mg dose group, respectively, with a HR of 1.05 (95 % CI) (0.81, 1.36).

  In a long-term cardio-renal outcome trial

  [seeClinical Studies 14.5]

  , in patients with chronic kidney disease, the occurrence of lower limb amputations was reported with event rates of 2.9, and 4.3 events per 1,000 patient-years in the placebo, and JARDIANCE 10 mg treatment arms, respectively. Amputation of the toe and mid-foot were most frequent (21 out of 28 JARDIANCE 10 mg treated patients with lower limb amputations), and some involving above and below the knee. Some patients had multiple amputations.

  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 about the importance of routine preventative foot care. Monitor patients receiving JARDIANCE 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 (e.g., angioedema) have occurred with JARDIANCE. If hypersensitivity reactions occur, discontinue JARDIANCE, treat promptly, and monitor until signs and symptoms resolve. (
  5.6 Hypersensitivity Reactions

  There have been postmarketing reports of serious hypersensitivity reactions (e.g., angioedema) in patients treated with JARDIANCE. If a hypersensitivity reaction occurs, discontinue JARDIANCE; treat promptly per standard of care, and monitor until signs and symptoms resolve. JARDIANCE is contraindicated in patients with hypersensitivity to empagliflozin or any of the excipients in JARDIANCE

  [seeContraindications (4)]

  .
  )

The following important adverse reactions are described below and elsewhere in the labeling:

• Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis
  [see

  5.1 Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis

  In patients with type 1 diabetes mellitus, JARDIANCE significantly increases the risk of diabetic ketoacidosis, a life-threatening event, beyond the background rate. In placebo-controlled trials of patients with type 1 diabetes mellitus, the risk of ketoacidosis was markedly increased in patients who received sodium glucose co-transporter 2 (SGLT2) inhibitors compared to patients who received placebo and fatal ketoacidosis has occurred with JARDIANCE. JARDIANCE is not indicated for glycemic control in patients with type 1 diabetes mellitus.

  Type 2 diabetes mellitus and pancreatic disorders (e.g., history of pancreatitis or pancreatic surgery) are also risk factors for ketoacidosis. There have been postmarketing reports of fatal events of ketoacidosis in patients with type 2 diabetes mellitus using SGLT2 inhibitors, including 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 are consistent with dehydration and severe metabolic acidosis and include nausea, vomiting, abdominal pain, generalized malaise, and shortness of breath. Blood glucose levels at presentation may be below those typically expected for diabetic ketoacidosis (e.g., less than 250 mg/dL). Ketoacidosis and glucosuria may persist longer than typically expected. Urinary glucose excretion persists for 3 days after discontinuing JARDIANCE

  [seeClinical Pharmacology (12.2)]

  ; however, there have been postmarketing reports of ketoacidosis and/or glucosuria lasting greater than 6 days and some up to 2 weeks after discontinuation of SGLT2 inhibitors.

  Consider ketone monitoring in patients with type 1 diabetes mellitus and consider ketone monitoring in others at risk for ketoacidosis if indicated by the clinical situation. Assess for ketoacidosis regardless of presenting blood glucose levels in patients who present with signs and symptoms consistent with severe metabolic acidosis. If ketoacidosis is suspected, discontinue JARDIANCE, promptly evaluate, and treat ketoacidosis, if confirmed. Monitor patients for resolution of ketoacidosis before restarting JARDIANCE.

  Withhold JARDIANCE, if possible, in temporary clinical situations that could predispose patients to ketoacidosis. Resume JARDIANCE when the patient is clinically stable and has resumed oral intake

  [seeDosage and Administration (2.3)]

  .

  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
  [see

  5.2 Volume Depletion

  JARDIANCE can cause intravascular volume depletion which may sometimes manifest as symptomatic hypotension or acute transient changes in creatinine

  [seeAdverse Reactions (6.1)]

  . There have been post-marketing reports of acute kidney injury, some requiring hospitalization and dialysis, in patients with type 2 diabetes mellitus receiving SGLT2 inhibitors, including JARDIANCE. Patients with impaired renal function (eGFR less than 60 mL/min/1.73 m²), elderly patients, or patients on loop diuretics may be at increased risk for volume depletion or hypotension. Before initiating JARDIANCE in patients with one or more of these characteristics, assess volume status and renal function. In patients with volume depletion, correct this condition before initiating JARDIANCE. Monitor for signs and symptoms of volume depletion, and renal function after initiating therapy.

  ]
• Genitourinary Infections, including Urosepsis, Pyelonephritis, Necrotizing Fasciitis of the Perineum (Fournier's Gangrene), and Genital Mycotic Infections
  [see

  5.3 Genitourinary Infections, including Urosepsis, Pyelonephritis, Necrotizing Fasciitis of the Perineum (Fournier's Gangrene), and Genital Mycotic Infections

  JARDIANCE increases urinary glucose excretion

  [seeClinical Pharmacology (12.2)]

  and increases the risk of genitourinary infections including urinary tract infections and genital mycotic infections in both male and female patients

  [seeAdverse Reactions (6.1)]

  .

  Serious genitourinary infections, including urosepsis, pyelonephritis, and necrotizing fasciitis of the perineum (Fournier's gangrene, a rare life-threatening infection requiring urgent surgical intervention), have occurred in patients with and without diabetes mellitus receiving SGLT2 inhibitors, including JARDIANCE

  [seeAdverse Reactions (6.2)].

  Cases have required hospitalization. In patients with Fournier's gangrene, serious outcomes have included multiple surgeries and death.

  Patients with a history of chronic or recurrent genitourinary infections are more likely to develop genitourinary infections when using JARDIANCE. Monitor patients for signs and symptoms of genitourinary infections and treat promptly, if indicated.

  Immediately evaluate patients presenting with pain or tenderness, erythema, or swelling in the genital or perineal area, along with fever or malaise, for necrotizing fasciitis. If suspected, discontinue JARDIANCE and promptly institute appropriate medical and/or surgical intervention.

  ]
• Hypoglycemia
  [see

  5.4 Hypoglycemia

  Insulin and insulin secretagogues are known to cause hypoglycemia. In adult patients, the risk of hypoglycemia may be increased when JARDIANCE is used in combination with insulin secretagogues (e.g., sulfonylurea) or insulin. In pediatric patients aged 10 years and older, the risk of hypoglycemia was higher with JARDIANCE regardless of insulin use

  [seeAdverse Reactions (6.1)]

  .

  The risk of hypoglycemia may be lowered by a reduction in the dose of sulfonylurea (or other concomitantly administered insulin secretagogues) or insulin. Inform patients using these concomitant medications and pediatric patients of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia.

  ]
• Hypersensitivity Reactions
  [see

  5.6 Hypersensitivity Reactions

  There have been postmarketing reports of serious hypersensitivity reactions (e.g., angioedema) in patients treated with JARDIANCE. If a hypersensitivity reaction occurs, discontinue JARDIANCE; treat promptly per standard of care, and monitor until signs and symptoms resolve. JARDIANCE is contraindicated in patients with hypersensitivity to empagliflozin or any of the excipients in JARDIANCE

  [seeContraindications (4)]

  .

  ]

See

JARDIANCE tablets for oral use contain empagliflozin, an inhibitor of the SGLT2.

The chemical name of empagliflozin is D-Glucitol,1,5-anhydro-1-C-[4-chloro-3-[[4-[[(3S)-tetrahydro-3-furanyl]oxy]phenyl]methyl]phenyl]-, (1S).

Its molecular formula is C₂₃H₂₇ClO₇ and the molecular weight is 450.91. The structural formula is:

Empagliflozin is a white to yellowish, non-hygroscopic powder. It is very slightly soluble in water, sparingly soluble in methanol, slightly soluble in ethanol and acetonitrile, soluble in 50% acetonitrile/water, and practically insoluble in toluene.

Each film-coated tablet of JARDIANCE contains 10 mg or 25 mg of empagliflozin (free base) and the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, hydroxypropyl cellulose, lactose monohydrate, magnesium stearate, and microcrystalline cellulose. In addition, the film coating contains the following inactive ingredients: ferric oxide yellow, hypromellose, polyethylene glycol, talc, and titanium dioxide.

Empagliflozin is an inhibitor of SGLT2, the predominant transporter responsible for reabsorption of glucose from the glomerular filtrate back into the circulation. By inhibiting SGLT2, empagliflozin reduces renal reabsorption of filtered glucose and lowers the renal threshold for glucose, and thereby increases urinary glucose excretion.

Empagliflozin also reduces sodium reabsorption and increases the delivery of sodium to the distal tubule. This may influence several physiological functions including, but not restricted to, increasing tubuloglomerular feedback and reducing intraglomerular pressure, lowering both pre- and afterload of the heart and downregulating sympathetic activity.

Carcinogenesis was evaluated in 2-year studies conducted in CD-1 mice and Wistar rats. Empagliflozin did not increase the incidence of tumors in female rats dosed at 100, 300, or 700 mg/kg/day (up to 72 times the exposure from the maximum clinical dose of 25 mg). In male rats, hemangiomas of the mesenteric lymph node were increased significantly at 700 mg/kg/day or approximately 42 times the exposure from a 25 mg clinical dose. Empagliflozin did not increase the incidence of tumors in female mice dosed at 100, 300, or 1,000 mg/kg/day (up to 62 times the exposure from a 25 mg clinical dose). Renal tubule adenomas and carcinomas were observed in male mice at 1,000 mg/kg/day, which is approximately 45 times the exposure of the maximum clinical dose of 25 mg. These tumors may be associated with a metabolic pathway predominantly present in the male mouse kidney.

JARDIANCE has been studied as monotherapy and in combination with metformin, sulfonylurea, pioglitazone, linagliptin, and insulin. JARDIANCE has also been studied in patients with type 2 diabetes mellitus with mild or moderate renal impairment.

In adult patients with type 2 diabetes mellitus, treatment with JARDIANCE reduced hemoglobin A1c (HbA1c), compared to placebo. The reduction in HbA1c for JARDIANCE compared with placebo was observed across subgroups including sex, race, geographic region, baseline BMI and duration of disease.

JARDIANCE tablets are available as follows:

Dispense in a well-closed container as defined in the USP.

Empagliflozin is an inhibitor of SGLT2, the predominant transporter responsible for reabsorption of glucose from the glomerular filtrate back into the circulation. By inhibiting SGLT2, empagliflozin reduces renal reabsorption of filtered glucose and lowers the renal threshold for glucose, and thereby increases urinary glucose excretion.

Empagliflozin also reduces sodium reabsorption and increases the delivery of sodium to the distal tubule. This may influence several physiological functions including, but not restricted to, increasing tubuloglomerular feedback and reducing intraglomerular pressure, lowering both pre- and afterload of the heart and downregulating sympathetic activity.