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 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 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 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 with type 2 diabetes mellitus. ( 1 ) Limitations of Use: Not recommended 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 adults with type 2 diabetes mellitus with an eGFR less than 30 mL/min/1.73 m 2 ( 1 ) Limitations of Use JARDIANCE is not recommended 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 adults 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.
Contraindications
Hypersensitivity to empagliflozin or any of the excipients in JARDIANCE, reactions such as angioedema have occurred [see Warnings and Precautions (5.7) ] . Patients on dialysis [see Use in Specific Populations (8.6) ] . Hypersensitivity to empagliflozin or any of the excipients in JARDIANCE ( 4 ) Patients on dialysis ( 4 )
Warnings and precautions
Ketoacidosis: Assess patients who present with signs and symptoms of metabolic acidosis for ketoacidosis, regardless of blood glucose level. If suspected, discontinue JARDIANCE, evaluate and treat promptly. Before initiating JARDIANCE, consider risk factors for ketoacidosis. Patients on JARDIANCE may require monitoring and temporary discontinuation of therapy in clinical situations known to predispose to ketoacidosis.
( 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 , 6.1 ) Urosepsis and Pyelonephritis: Evaluate patients for signs and symptoms of urinary tract infections and treat promptly, if indicated ( 5.3 ) Hypoglycemia: Consider lowering the dose of insulin secretagogue or insulin to reduce the risk of hypoglycemia when initiating JARDIANCE ( 5.4 ) Necrotizing Fasciitis of the Perineum (Fournier's Gangrene): Serious, life-threatening cases have occurred in both females and males.
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. ( 5.5 ) Genital Mycotic Infections: Monitor and treat as appropriate ( 5.6 ) 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.
( 5.7 )
5.1Ketoacidosis Reports
of ketoacidosis, a serious life-threatening condition requiring urgent hospitalization have been identified in clinical trials and postmarketing surveillance in patients with type 1 and type 2 diabetes mellitus receiving sodium glucose co-transporter-2 (SGLT2) inhibitors, including JARDIANCE. Fatal cases of ketoacidosis have been reported in patients taking JARDIANCE. In placebo-controlled trials of patients with type 1 diabetes, the risk of ketoacidosis was increased in patients who received SGLT2 inhibitors compared to patients who received placebo.
JARDIANCE is not indicated for the treatment of patients with type 1 diabetes mellitus [see Indications and Usage (1) ] . Patients treated with JARDIANCE who present with signs and symptoms consistent with severe metabolic acidosis should be assessed for ketoacidosis regardless of presenting blood glucose levels, as ketoacidosis associated with JARDIANCE may be present even if blood glucose levels are less than 250 mg/dL.
If ketoacidosis is suspected, JARDIANCE should be discontinued, patient should be evaluated, and prompt treatment should be instituted. Treatment of ketoacidosis may require insulin, fluid and carbohydrate replacement. In many of the postmarketing reports, and particularly in patients with type 1 diabetes, the presence of ketoacidosis was not immediately recognized and institution of treatment was delayed because presenting blood glucose levels were below those typically expected for diabetic ketoacidosis (often less than 250 mg/dL).
Signs and symptoms at presentation were consistent with dehydration and severe metabolic acidosis and included nausea, vomiting, abdominal pain, generalized malaise, and shortness of breath. In some but not all cases, factors predisposing to ketoacidosis such as insulin dose reduction, acute febrile illness, reduced caloric intake, surgery, pancreatic disorders suggesting insulin deficiency (e.g., type 1 diabetes, history of pancreatitis or pancreatic surgery), and alcohol abuse were identified.
Before initiating JARDIANCE, consider factors in the patient history that may predispose to ketoacidosis including pancreatic insulin deficiency from any cause, caloric restriction, and alcohol abuse. For patients who undergo scheduled surgery, consider temporarily discontinuing JARDIANCE for at least 3 days prior to surgery [see Clinical Pharmacology (12.2 , 12.3) ] . Consider monitoring for ketoacidosis and temporarily discontinuing JARDIANCE in other clinical situations known to predispose to ketoacidosis (e.g., prolonged fasting due to acute illness or post-surgery).
Ensure risk factors for ketoacidosis are resolved prior to restarting JARDIANCE. Educate patients on the signs and symptoms of ketoacidosis and instruct patients to discontinue JARDIANCE and seek medical attention immediately if signs and symptoms occur.
5.2Volume 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.
5.3Urosepsis and Pyelonephritis
There have been reports of serious urinary tract infections including urosepsis and pyelonephritis requiring hospitalization in patients receiving SGLT2 inhibitors, including JARDIANCE. Treatment with SGLT2 inhibitors increases the risk for urinary tract infections. Evaluate patients for signs and symptoms of urinary tract infections and treat promptly, if indicated [see Adverse Reactions (6) ] .
5.4Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues Insulin
and insulin secretagogues are known to cause hypoglycemia. The risk of hypoglycemia is increased when JARDIANCE is used in combination with insulin secretagogues (e.g., sulfonylurea) or insulin [see Adverse Reactions (6.1) ] . Therefore, a lower dose of the insulin secretagogue or insulin may be required to reduce the risk of hypoglycemia when used in combination with JARDIANCE.
5.5Necrotizing Fasciitis of the Perineum (Fournier's Gangrene) Reports
of necrotizing fasciitis of the perineum (Fournier's gangrene), a rare but serious and life-threatening necrotizing infection requiring urgent surgical intervention, have been identified in patients with diabetes mellitus receiving SGLT2 inhibitors, including JARDIANCE. Cases have been reported in both females and males. Serious outcomes have included hospitalization, multiple surgeries, and death. Patients treated with JARDIANCE presenting with pain or tenderness, erythema, or swelling in the genital or perineal area, along with fever or malaise, should be assessed for necrotizing fasciitis.
If suspected, start treatment immediately with broad-spectrum antibiotics and, if necessary, surgical debridement. Discontinue JARDIANCE, closely monitor blood glucose levels, and provide appropriate alternative therapy for glycemic control.
5.6Genital Mycotic Infections
JARDIANCE increases the risk for genital mycotic infections [see Adverse Reactions (6.1) ] . Patients with a history of chronic or recurrent genital mycotic infections were more likely to develop genital mycotic infections. Monitor and treat as appropriate.
5.7Hypersensitivity 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 [see Contraindications (4) ] .
Interactions
Table 3 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 doses 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 )
Pregnancy and breastfeeding
8.1Pregnancy 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).
Adverse reactions
The following important adverse reactions are described below and elsewhere in the labeling: Ketoacidosis [see Warnings and Precautions (5.1) ] Volume Depletion [see Warnings and Precautions (5.2) ] Urosepsis and Pyelonephritis [see Warnings and Precautions (5.3) ] Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues [see Warnings and Precautions (5.4) ] Necrotizing Fasciitis of the Perineum (Fournier's Gangrene) [see Warnings and Precautions (5.5) ] Genital Mycotic Infections [see Warnings and Precautions (5.6) ] Hypersensitivity Reactions [see Warnings and Precautions (5.7) ] 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 .
6.1Clinical 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 patients with type 2 diabetes mellitus and in patients with heart failure. The overall safety profile of JARDIANCE was generally consistent across the studied indications.
Clinical Trials in Patients with Type 2 Diabetes Mellitus The data in Table 1 are derived from a pool of four 24-week placebo-controlled trials and 18-week data from a placebo-controlled trial with insulin in patients with type 2 diabetes. JARDIANCE was used as monotherapy in one trial and as add-on therapy in four trials [see Clinical Studies (14) ] . These data reflect exposure of 1976 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 more than 5 years and had a mean hemoglobin A1c (HbA1c) of 8%. Established microvascular complications of diabetes 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 1 shows common adverse reactions (excluding hypoglycemia) associated with the use of JARDIANCE. The adverse reactions were not present at baseline, occurred more commonly on JARDIANCE than on placebo and occurred in greater than or equal to 2% of patients treated with JARDIANCE 10 mg or JARDIANCE 25 mg.
Table 1 Adverse Reactions Reported in ≥2% of Patients Treated with JARDIANCE and Greater than Placebo in Pooled Placebo-Controlled Clinical Studies 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
1.1Thirst
(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, 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, adverse reactions of increased urination (e.g., polyuria, pollakiuria, and nocturia) occurred more frequently on JARDIANCE than on placebo (see Table 1 ). 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 The incidence of hypoglycemia by study is shown in Table 2 . The incidence of hypoglycemia increased when JARDIANCE was administered with insulin or sulfonylurea. Table 2 Incidence of Overall a and Severe b Hypoglycemic Events in Placebo-Controlled Clinical Studies c a Overall hypoglycemic events: plasma or capillary glucose of less than or equal to 70 mg/dL b Severe hypoglycemic events: requiring assistance regardless of blood glucose c Treated set (patients who had received at least one dose of study drug) d Insulin dose could not be adjusted during the initial 18-week treatment period Monotherapy (24 weeks) Placebo (n=229) JARDIANCE 10 mg (n=224) JARDIANCE 25 mg (n=223) Overall (%) 0.4 0.4
0.5 Genital Mycotic Infections In the pool of five placebo-controlled clinical trials, the incidence of genital mycotic infections (e.g., vaginal mycotic infection, vaginal infection, genital infection fungal, vulvovaginal candidiasis, and vulvitis) was increased in patients treated with JARDIANCE compared to placebo, occurring in 0.9%, 4.1%, and 3.7% of patients randomized to placebo, JARDIANCE 10 mg, and JARDIANCE 25 mg, respectively.
Discontinuation from study due to genital infection occurred in 0% of placebo-treated patients and 0.
Our copy of this section ends here. The full text is in the official label at the FDA. Open Drugs@FDA
Composition
Active ingredients
EMPAGLIFLOZIN 25MG
Strengths and forms
The FDA lists each strength of a product separately; these pages share one label.
Prognia shows this product information for reference and learning. It is not treatment advice and can lag behind the official text. Always check the current product information and local protocols before prescribing.
