Jardiance

Empagliflozin · Tablet, Film Coated · Oral

Prescription (Rx) Sodium-Glucose Cotransporter 2 Inhibitor 2 recalls

Uses

1 INDICATIONS AND USAGE 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. JARDIANCE is a sodium-glucose co-transporter 2 (SGLT2) inhibitor indicated: To reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure. ( 1 ) 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. ( 1 ) To reduce the risk of cardiovascular death in adults with type 2 diabetes mellitus and established cardiovascular disease. ( 1 ) 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. ( 1 ) Limitations of Use: Not recommended for use to improve glycemic control in patients with type 1 diabetes mellitus. It may increase the risk of diabetic ketoacidosis in these patients. ( 1 ) Not recommended for use to improve glycemic control in patients with type 2 diabetes mellitus with an eGFR less than 30 mL/min/1.73 m 2 . ( 1 ) Not recommended for the treatment of chronic kidney disease in patients with polycystic kidney disease or patients requiring or with a recent history of intravenous immunosuppressive therapy or greater than 45 mg of prednisone or equivalent for kidney disease. JARDIANCE is not expected to be effective in these populations. ( 1 ) Limitations of Use JARDIANCE is not recommended for use to improve glycemic control in patients with type 1 diabetes mellitus. It may increase the risk of diabetic ketoacidosis in these patients [see Warnings and Precautions (5.1) ] . JARDIANCE is not recommended for use to improve glycemic control in patients with type 2 diabetes mellitus with an eGFR less than 30 mL/min/1.73 m 2 . JARDIANCE is likely to be ineffective in this setting based upon its mechanism of action. JARDIANCE is not recommended for the treatment of chronic kidney disease in patients with polycystic kidney disease or patients requiring or with a recent history of intravenous immunosuppressive therapy or greater than 45 mg of prednisone or equivalent for kidney disease [see Clinical Studies (14.5) ] . JARDIANCE is not expected to be effective in these populations.

Dosage and administration

Assess renal function before initiating and as clinically indicated. Assess volume status and correct volume depletion before initiating. ( 2.1 ) Recommended dosage is 10 mg orally once daily in the morning, taken with or without food. ( 2.2 ) For additional glycemic control, dosage may be increased to 25 mg orally once daily in patients tolerating JARDIANCE. ( 2.2 ) Withhold JARDIANCE for at least 3 days, if possible, prior to surgery or procedures associated with prolonged fasting. ( 2.3 ) 2.1 Testing Prior to Initiation of JARDIANCE Assess renal function before initiating JARDIANCE and as clinically indicated [see Warnings and Precautions (5.2) ] . Use for glycemic control is not recommended in patients with an eGFR less than 30 mL/min/1.73 m 2 [see Use in Specific Populations (8.6) ]. Assess volume status. In patients with volume depletion, correct this condition before initiating JARDIANCE [see Warnings and Precautions (5.2) and Use in Specific Populations (8.5 , 8.6) ]. 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. 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 [see Warnings and Precautions (5.1) and Clinical Pharmacology (12.2) ]. 2.4 Recommendations Regarding Missed Dose If a dose is missed, instruct patients to take the dose as soon as possible. Advise patients not to double up the next dose.

Dosage forms and strengths

3 DOSAGE FORMS AND STRENGTHS 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. Tablets: 10 mg, 25 mg ( 3 )

Contraindications

4 CONTRAINDICATIONS JARDIANCE is contraindicated in patients: with a hypersensitivity to empagliflozin or any of the excipients in JARDIANCE, reactions such as angioedema have occurred [see Warnings and Precautions (5.6) ] . Hypersensitivity to empagliflozin or any of the excipients in JARDIANCE. ( 4 )

Warnings and precautions

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 ) 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 ) 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 ) 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 ) Lower Limb Amputation: Monitor patients for infections or ulcers of lower limbs, and institute appropriate treatment ( 5.5 ) 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 ) 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 [see Clinical 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 [see Dosage 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. 5.2 Volume Depletion JARDIANCE can cause intravascular volume depletion which may sometimes manifest as symptomatic hypotension or acute transient changes in creatinine [see Adverse 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 m 2 ), 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.

Side effects

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 Warnings and Precautions (5.1) ] Volume Depletion [see Warnings and Precautions (5.2) ] Genitourinary Infections, including Urosepsis, Pyelonephritis, Necrotizing Fasciitis of the Perineum (Fournier's Gangrene), and Genital Mycotic Infections [see Warnings and Precautions (5.3) ] Hypoglycemia [see Warnings and Precautions (5.4) ] Hypersensitivity Reactions [see Warnings and Precautions (5.6) ] Most common adverse reactions (5% or greater incidence) were urinary tract infections and female genital mycotic infections ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Boehringer Ingelheim Pharmaceuticals, Inc. at 1-800-542-6257 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. JARDIANCE has been evaluated in clinical trials in adult and pediatric patients aged 10 to 17 years with type 2 diabetes mellitus, in adults with heart failure, and in adults with chronic kidney disease. The overall safety profile of JARDIANCE was generally consistent across the studied indications. Clinical Trials in Adults with Type 2 Diabetes Mellitus The data in Table 2 are derived from a pool of four 24-week placebo-controlled trials and 18-week data from a placebo-controlled trial with insulin in adult patients with type 2 diabetes mellitus. JARDIANCE was used as monotherapy in one trial and as add-on therapy in four trials [see Clinical Studies (14.1) ] . These data reflect exposure of 1,976 adult patients to JARDIANCE with a mean exposure duration of approximately 23 weeks. Patients received placebo (N=995), JARDIANCE 10 mg (N=999), or JARDIANCE 25 mg (N=977) once daily. The mean age of the population was 56 years and 3% were older than 75 years of age. More than half (55%) of the population was male; 46% were White, 50% were Asian, and 3% were Black or African American. At baseline, 57% of the population had diabetes mellitus more than 5 years and had a mean hemoglobin A1c (HbA1c) of 8%. Established microvascular complications of diabetes mellitus at baseline included diabetic nephropathy (7%), retinopathy (8%), or neuropathy (16%). Baseline renal function was normal or mildly impaired in 91% of patients and moderately impaired in 9% of patients (mean eGFR 86.8 mL/min/1.73 m 2 ). Table 2 shows adverse reactions (excluding hypoglycemia) that were not present at baseline, occurred more commonly in JARDIANCE-treated patients than on placebo and occurred in greater than or equal to 2% JARDIANCE-treated patients. Table 2 Adverse Reactions Reported in ≥2% of Adults with Type 2 Diabetes Mellitus Treated with JARDIANCE and Greater than Placebo in Pooled Placebo-Controlled Clinical Trials of JARDIANCE Monotherapy or Combination Therapy Adverse Reactions Placebo (%) N=995 JARDIANCE 10 mg (%) N=999 JARDIANCE 25 mg (%) N=977 a Predefined adverse event grouping, including, but not limited to, urinary tract infection, asymptomatic bacteriuria, cystitis b Female genital mycotic infections include the following adverse reactions: vulvovaginal mycotic infection, vaginal infection, vulvitis, vulvovaginal candidiasis, genital infection, genital candidiasis, genital infection fungal, genitourinary tract infection, vulvovaginitis, cervicitis, urogenital infection fungal, vaginitis bacterial. Percentages calculated with the number of female subjects in each group as denominator: placebo (N=481), JARDIANCE 10 mg (N=443), JARDIANCE 25 mg (N=420). c Predefined adverse event grouping, including, but not limited to, polyuria, pollakiuria, and nocturia d Male genital mycotic infections include the following adverse reactions: balanoposthitis, balanitis, genital infections fungal, genitourinary tract infection, balanitis candida, scrotal abscess, penile infection. Percentages calculated with the number of male subjects in each group as denominator: placebo (N=514), JARDIANCE 10 mg (N=556), JARDIANCE 25 mg (N=557). Urinary tract infection a 7.6 9.3 7.6 Female genital mycotic infections b 1.5 5.4 6.4 Upper respiratory tract infection 3.8 3.1 4.0 Increased urination c 1.0 3.4 3.2 Dyslipidemia 3.4 3.9 2.9 Arthralgia 2.2 2.4 2.3 Male genital mycotic infections d 0.4 3.1 1.6 Nausea 1.4 2.3 1.1 Thirst (including polydipsia) was reported in 0%, 1.7%, and 1.5% for placebo, JARDIANCE 10 mg, and JARDIANCE 25 mg, respectively. Volume Depletion JARDIANCE causes an osmotic diuresis, which may lead to intravascular volume contraction and adverse reactions related to volume depletion. In the pool of five placebo-controlled clinical trials in adults, adverse reactions related to volume depletion (e.g., blood pressure (ambulatory) decreased, blood pressure systolic decreased, dehydration, hypotension, hypovolemia, orthostatic hypotension, and syncope) were reported by 0.3%, 0.5%, and 0.3% of patients treated with placebo, JARDIANCE 10 mg, and JARDIANCE 25 mg, respectively. JARDIANCE may increase the risk of hypotension in patients at risk for volume contraction [see Use in Specific Populations (8.5 , 8.6) ]. Increased Urination In the pool of five placebo-controlled clinical trials in adults, adverse reactions of increased urination (e.g., polyuria, pollakiuria, and nocturia) occurred more frequently on JARDIANCE than on placebo (see Table 2 ). Specifically, nocturia was reported by 0.4%, 0.3%, and 0.8% of patients treated with placebo, JARDIANCE 10 mg, and JARDIANCE 25 mg, respectively. Hypoglycemia in Clinical Trials for Glycemic Control in Adults with Type 2 Diabetes Mellitus The incidence of hypoglycemia in adults by trial is shown in Table 3 .

Drug interactions

See Table 4 for clinically relevant interactions with JARDIANCE. Table 4 Clinically Relevant Interactions with JARDIANCE Diuretics Clinical Impact Coadministration of empagliflozin with diuretics resulted in increased urine volume and frequency of voids, which might enhance the potential for volume depletion. Intervention Before initiating JARDIANCE, 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. Insulin or Insulin Secretagogues Clinical Impact The risk of hypoglycemia is increased when JARDIANCE is used in combination with insulin secretagogues (e.g., sulfonylurea) or insulin. Intervention Coadministration of JARDIANCE with an insulin secretagogue (e.g., sulfonylurea) or insulin may require lower dosages of the insulin secretagogue or insulin to reduce the risk of hypoglycemia. Lithium Clinical Impact Concomitant use of an SGLT2 inhibitor with lithium may decrease serum lithium concentrations. Intervention Monitor serum lithium concentration more frequently during JARDIANCE initiation and dosage changes. Positive Urine Glucose Test Clinical Impact SGLT2 inhibitors increase urinary glucose excretion and will lead to positive urine glucose tests. Intervention Monitoring glycemic control with urine glucose tests is not recommended in patients taking SGLT2 inhibitors. Use alternative methods to monitor glycemic control. Interference with 1,5-anhydroglucitol (1,5-AG) Assay Clinical Impact Measurements of 1,5-AG are unreliable in assessing glycemic control in patients taking SGLT2 inhibitors. Intervention Monitoring glycemic control with 1,5-AG assay is not recommended. Use alternative methods to monitor glycemic control. See full prescribing information for information on drug interactions and interference of JARDIANCE with laboratory tests. ( 7 )

Use in specific populations

Pregnancy: Advise females of the potential risk to a fetus especially during the second and third trimesters. ( 8.1 ) Lactation: Not recommended when breastfeeding. ( 8.2 ) Geriatric Patients: Higher incidence of adverse reactions related to volume depletion and reduced renal function. ( 8.5 ) Renal Impairment: Higher incidence of adverse reactions related to reduced renal function. ( 8.6 ) 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 [see Clinical 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 [see Data ] . 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). 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 [see Data ] . 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. 8.4 Pediatric Use The safety and effectiveness of JARDIANCE as an adjunct to diet and exercise to improve glycemic control in type 2 diabetes mellitus have been established in pediatric patients aged 10 years and older. Use of JARDIANCE for this indication is supported by evidence from a 26-week double-blind, placebo-controlled clinical trial, with a double-blind active treatment safety extension period of up to 52 weeks in 157 pediatric patients aged 10 to 17 years with type 2 diabetes mellitus and a pediatric pharmacokinetic study [see Clinical Pharmacology (12.3) and Clinical Studies (14.2) ] . The safety profile of pediatric patients treated with JARDIANCE was similar to that observed in adults with type 2 diabetes mellitus, with the exception of hypoglycemia risk which was higher in pediatric patients treated with JARDIANCE regardless of concomitant insulin use [see Warnings and Precautions (5.4) and Adverse Reactions (6.1) ].

Pregnancy

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 [see Clinical 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 [see Data ] . 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).

Pediatric use

8.4 Pediatric Use The safety and effectiveness of JARDIANCE as an adjunct to diet and exercise to improve glycemic control in type 2 diabetes mellitus have been established in pediatric patients aged 10 years and older. Use of JARDIANCE for this indication is supported by evidence from a 26-week double-blind, placebo-controlled clinical trial, with a double-blind active treatment safety extension period of up to 52 weeks in 157 pediatric patients aged 10 to 17 years with type 2 diabetes mellitus and a pediatric pharmacokinetic study [see Clinical Pharmacology (12.3) and Clinical Studies (14.2) ] . The safety profile of pediatric patients treated with JARDIANCE was similar to that observed in adults with type 2 diabetes mellitus, with the exception of hypoglycemia risk which was higher in pediatric patients treated with JARDIANCE regardless of concomitant insulin use [see Warnings and Precautions (5.4) and Adverse Reactions (6.1) ]. The safety and effectiveness of JARDIANCE have not been established in pediatric patients less than 10 years of age as an adjunct to diet and exercise to improve glycemic control in type 2 diabetes mellitus. The safety and effectiveness of JARDIANCE have not been established in pediatric patients to reduce the risk of: cardiovascular death and hospitalization for heart failure in patients with heart failure. sustained decline in eGFR, end-stage kidney disease, cardiovascular death, and hospitalization in patients with chronic kidney disease at risk of progression. cardiovascular death in patients with type 2 diabetes mellitus and established cardiovascular disease.

Geriatric use

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 [see Use 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 [see Warnings and Precautions (5.2) and Adverse 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.

Overdosage

In the event of an overdose with JARDIANCE, consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdosage management recommendations. Removal of empagliflozin by hemodialysis has not been studied.

Description

11 DESCRIPTION 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 C 23 H 27 ClO 7 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. Chemical Structure

Mechanism of action

12.1 Mechanism of Action 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.

How supplied

16 HOW SUPPLIED/STORAGE AND HANDLING JARDIANCE tablets are available as follows: 10 mg tablets: 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. Bottles of 30 (NDC 0597-0152-30) Bottles of 90 (NDC 0597-0152-90) Cartons containing 3 blister cards of 10 tablets each (3 × 10) (NDC 0597-0152-37), institutional pack. 25 mg tablets: pale yellow, oval, biconvex film-coated tablets, debossed with "S 25" on one side and the Boehringer Ingelheim company symbol on the other side. Bottles of 30 (NDC 0597-0153-30) Bottles of 90 (NDC 0597-0153-90) Cartons containing 3 blister cards of 10 tablets each (3 × 10) (NDC 0597-0153-37), institutional pack. Dispense in a well-closed container as defined in the USP. Storage Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

Storage

Storage Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

Patient information

Advise the patient to read the FDA-approved patient labeling (Medication Guide). Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis In patients with type 1 diabetes mellitus, inform them that using JARDIANCE can increase their risk of life-threatening diabetic ketoacidosis and that fatal ketoacidosis has occurred. For all other patients, inform them that JARDIANCE can cause potentially fatal ketoacidosis and that type 2 diabetes mellitus and pancreatic disorders (e.g., history of pancreatitis or pancreatic surgery) are risk factors. Educate all patients on precipitating factors (such as insulin dose reduction or missed insulin doses, infection, reduced caloric intake, ketogenic diet, surgery, dehydration, and alcohol abuse) and symptoms of ketoacidosis (including nausea, vomiting, abdominal pain, tiredness, and labored breathing). Inform patients that blood glucose may be normal even in the presence of ketoacidosis. Advise patients that they may be asked to monitor ketones. If symptoms of ketoacidosis occur, instruct patients to discontinue JARDIANCE and seek medical attention immediately [see Warnings and Precautions (5.1) ] . Volume Depletion Inform patients that symptomatic hypotension may occur with JARDIANCE and advise them to contact their healthcare provider if they experience such symptoms [see Warnings and Precautions (5.2) ] . Inform patients that dehydration may increase the risk for hypotension, and to maintain adequate fluid intake. Genitourinary Infections, including Urosepsis, Pyelonephritis, Necrotizing Fasciitis of the Perineum (Fournier's Gangrene), and Genital Mycotic Infections Counsel patients that genitourinary infections may occur when taking JARDIANCE and may become serious. Educate them on the symptoms and advise them to seek medical advice if symptoms occur. Specifically, advise patients to promptly seek medical attention if they develop pain or tenderness, redness, or swelling of the genitals or the area from the genitals back to the rectum, along with a fever above 100.4°F or malaise [see Warnings and Precautions (5.3) ] . Hypoglycemia Inform patients that hypoglycemia has been reported when JARDIANCE is used with insulin secretagogues or insulin. Hypoglycemia may occur in pediatric patients regardless of concomitant antidiabetic treatment. Educate patients or caregivers on the signs and symptoms of hypoglycemia [see Warnings and Precautions (5.4) ] . Lower Limb Amputation Counsel patients about the importance of routine preventative foot care. Instruct patients to monitor for new pain or tenderness, sores or ulcers, or infections involving the leg or foot and to seek medical advice immediately if such signs or symptoms develop [see Warnings and Precautions (5.5) ] . Hypersensitivity Reactions Inform patients that serious hypersensitivity reactions, such as urticaria and angioedema, have been reported with JARDIANCE. Advise patients to report immediately any skin reaction or angioedema, and to discontinue drug until they have consulted prescribing healthcare provider [see Warnings and Precautions (5.6) ] . Laboratory Tests Inform patients that elevated glucose in urinalysis is expected when taking JARDIANCE [see Drug Interactions (7) ] . Pregnancy Advise pregnant patients, and patients of reproductive potential, of the potential risk to a fetus with treatment with JARDIANCE [see Use in Specific Populations (8.1) ] . Instruct patients to report pregnancies to their healthcare provider as soon as possible. Lactation Advise patients that breastfeeding is not recommended during treatment with JARDIANCE [see Use in Specific Populations (8.2) ]. Missed Dose Instruct patients to take JARDIANCE only as prescribed. If a dose is missed, it should be taken as soon as the patient remembers. Advise patients not to double their next dose [see Dosage and Administration (2.4) ] .

Label text from the FDA structured product label by Boehringer Ingelheim Pharmaceuticals, Inc. (revised Jan 30, 2026). Long sections are shortened; the complete label is on DailyMed.

Active ingredients

Empagliflozin in 11 products

Jardiance NDC products (11)

NDC	Strength & form	Labeler	Type
50090-4384	Empagliflozin 25 mg/1 Tablet, Film Coated	A-S Medication Solutions	NDA
50090-4492	Empagliflozin 10 mg/1 Tablet, Film Coated	A-S Medication Solutions	NDA
50090-6452	Empagliflozin 10 mg/1 Tablet, Film Coated	A-S Medication Solutions	NDA
50090-6457	Empagliflozin 25 mg/1 Tablet, Film Coated	A-S Medication Solutions	NDA
71610-177	Empagliflozin 25 mg/1 Tablet, Film Coated	Aphena Pharma Solutions - Tennessee, LLC	NDA
71610-900	Empagliflozin 10 mg/1 Tablet, Film Coated	Aphena Pharma Solutions - Tennessee, LLC	NDA
0597-0152	Empagliflozin 10 mg/1 Tablet, Film Coated	Boehringer Ingelheim Pharmaceuticals, Inc.	NDA
0597-0153	Empagliflozin 25 mg/1 Tablet, Film Coated	Boehringer Ingelheim Pharmaceuticals, Inc.	NDA
55154-0411	Empagliflozin 10 mg/1 Tablet, Film Coated	Cardinal Health 107, LLC	NDA
55154-0412	Empagliflozin 25 mg/1 Tablet, Film Coated	Cardinal Health 107, LLC	NDA
67296-2324	Empagliflozin 25 mg/1 Tablet, Film Coated	Redpharm Drug	NDA

Jardiance recalls

D-0185-2024 Jan 3, 2024 · Class II · Terminated
CGMP Deviations: Products were exposed to temperatures outside of the products labeled storage conditions.
D-0468-2023 Mar 29, 2023 · Class II · Terminated
Labeling: Label Mix-up

Frequently asked questions

What is Jardiance used for?

What are the side effects of Jardiance?

Who makes Jardiance?

Jardiance is listed by 5 labelers in the FDA NDC directory, including A-S Medication Solutions, Aphena Pharma Solutions - Tennessee, LLC, Boehringer Ingelheim Pharmaceuticals, Inc., Cardinal Health 107, LLC.

Has Jardiance been recalled?

The FDA enforcement database lists 2 recalls for Jardiance, most recently D-0185-2024 (class ii): CGMP Deviations: Products were exposed to temperatures outside of the products labeled storage conditions.