Skip to Content

Jardiance

Generic Name: Empagliflozin
Class: Sodium-glucose Cotransporter 2 (SGLT2) Inhibitors
VA Class: 0000
Chemical Name: (1S)-1,5-Anhydro-1-C-[4-chloro-3-[[4-[[(3S)-tetrahydro-3-furanyl]oxy]phenyl]methyl]phenyl]-d-glucitol
Molecular Formula: C23H27ClO7
CAS Number: 864070-44-0

Medically reviewed by Drugs.com. Last updated on Nov 18, 2019.

Introduction

Antidiabetic agent; sodium-glucose cotransporter 2 (SGLT2) inhibitor.1

Uses for Jardiance

Type 2 Diabetes Mellitus

Used as monotherapy as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus.1 2

Used to reduce the risk of cardiovascular death in patients with type 2 diabetes mellitus and established cardiovascular disease.1 90

May have beneficial effects on renal function; reduction of the risk of CKD progression demonstrated in clinical studies.91

Used in combination with other antidiabetic agents (e.g., metformin, a sulfonylurea, a peroxisome proliferator-activated receptorγ [PPARγ] agonist [thiazolidinedione], a dipeptidylpeptidase-4 [DPP-4] inhibitor) or insulin as an adjunct to diet and exercise in patients with type 2 diabetes mellitus who have not achieved adequate glycemic control.1 3 4 5 6 7 8 9

Used in fixed combination with immediate- or extended-release metformin hydrochloride or linagliptin as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus when treatment with both drugs is appropriate.70 72 74

Current guidelines for the treatment of type 2 diabetes mellitus generally recommend metformin as first-line therapy in addition to lifestyle modifications due to its well-established safety and efficacy (e.g., beneficial effects on glycosylated hemoglobin [hemoglobin A1c; HbA1c], weight, and cardiovascular mortality).598 604 Consider patient's comorbidities when selecting additional antidiabetic agents.598 604

Patients with type 2 diabetes mellitus who have established atherosclerotic cardiovascular disease (ASCVD) should receive a drug with demonstrated cardiovascular disease benefit (e.g., glucagon-like peptide-1 [GLP-1] receptor agonist [e.g., liraglutide], SGLT2 inhibitor [e.g., empagliflozin]).604 In patients with ASCVD and heart failure or with an increased risk of heart failure, an SGLT2 inhibitor with demonstrated cardiovascular benefit may be preferred.604

In patients with type 2 diabetes mellitus and CKD, an SGLT2 inhibitor or GLP-1 receptor agonist with demonstrated ability to reduce the risk of CKD progression, cardiovascular events, or both (e.g., canagliflozin, empagliflozin, liraglutide) should be considered.604

In patients without ASCVD, heart failure, or CKD, the decision regarding the addition of other antidiabetic agents (e.g., sulfonylurea, thiazolidinedione, DPP-4 inhibitor, SGLT2 inhibitor, GLP-1 receptor agonist, basal insulin) should be based on drug-specific effects and individual patient factors.604

Not indicated for type 1 diabetes mellitus or treatment of diabetic ketoacidosis.1

Jardiance Dosage and Administration

General

  • Correct volume depletion prior to initiating empagliflozin; assess renal function prior to treatment and periodically thereafter.1

Administration

Oral Administration

Administer empagliflozin or the fixed combination of empagliflozin and linagliptin once daily in the morning, with or without food.1 70

Administer the fixed combination of empagliflozin and immediate-release metformin hydrochloride twice daily with meals.72

Administer the fixed combination of empagliflozin and extended-release metformin hydrochloride once daily with the morning meal; swallow tablet whole (do not crush, chew, or cut).74

If a dose is missed, take missed dose as soon as it is remembered followed by resumption of the regular schedule.1 14 71 72 73 74 75 If the missed dose is not remembered until it is almost time for the next dose, skip the missed dose and resume the regular schedule; do not double the dose to replace a missed dose.1 14 71 72 73 74 75

Dosage

Adults

Type 2 Diabetes Mellitus
Empagliflozin Monotherapy
Oral

Initially, 10 mg once daily in the morning.1

If well tolerated, may increase dosage to 25 mg once daily.1

Empagliflozin/Linagliptin Fixed-combination Therapy
Oral

Initially, 10 mg of empagliflozin and 5 mg of linagliptin once daily in the morning.70

If well tolerated, may increase dosage to 25 mg of empagliflozin and 5 mg of linagliptin once daily.70

Empagliflozin/Immediate-release Metformin Hydrochloride Fixed-combination Therapy
Oral

Individualize dosage of empagliflozin in fixed combination with immediate-release metformin hydrochloride based on the patient's current antidiabetic regimen.72 May increase dosage gradually based on effectiveness and tolerability up to a maximum daily dosage of 25 mg of empagliflozin and 2 g of immediate-release metformin hydrochloride.72

Patients currently receiving metformin hydrochloride: Initially, 10 mg of empagliflozin and a total daily dosage of immediate-release metformin hydrochloride similar to the patient's existing dosage, administered in 2 divided doses.72

Patients currently receiving empagliflozin: Initially, same daily dosage of empagliflozin and 1 g of immediate-release metformin hydrochloride, administered in 2 divided doses.72

Patients currently receiving both empagliflozin and metformin hydrochloride: Initially, same daily dosage of empagliflozin and a total daily dosage of immediate-release metformin hydrochloride similar to the patient's existing dosage, administered in 2 divided doses.72

Empagliflozin/Extended-release Metformin Hydrochloride Fixed-combination Therapy
Oral

Individualize dosage of empagliflozin in fixed combination with extended-release metformin hydrochloride based on the patient's current antidiabetic regimen.74 May increase dosage gradually based on effectiveness and tolerability up to a daily maximum of 25 mg of empagliflozin and 2 g of extended-release metformin hydrochloride.74

Patients currently receiving metformin hydrochloride: Initially, 10 mg of empagliflozin and a total daily dosage of extended-release metformin hydrochloride similar to the patient's existing dosage, administered once daily.74

Patients currently receiving empagliflozin: Initially, same daily dosage of empagliflozin and 1 g of extended-release metformin hydrochloride, administered once daily.74

Patients currently receiving both empagliflozin and metformin hydrochloride: Initially, same daily dosage of empagliflozin and a total daily dosage of extended-release metformin hydrochloride similar to the patient's existing dosage, administered once daily.74

Special Populations

Hepatic Impairment

Empagliflozin Monotherapy

Mild, moderate, or severe: No dosage adjustment necessary.13

Empagliflozin/Linagliptin Fixed-combination Therapy

May be used in patients with hepatic impairment.70

Empagliflozin/Metformin Hydrochloride Fixed-combination Therapy

Use of the fixed-combination preparation of empagliflozin and immediate- or extended-release metformin hydrochloride not recommended.72 74

Renal Impairment

Empagliflozin Monotherapy

Estimated GFR (eGFR) ≥45 mL/minute per 1.73 m2: No dosage adjustment necessary.1

eGFR <45 mL/minute per 1.73 m2: Do not initiate drug.1 Discontinue drug if eGFR is persistently <45 mL/minute per 1.73 m2.1 (See Renal Impairment under Cautions.)

Empagliflozin/Linagliptin Fixed-combination Therapy

eGFR ≥45 mL/minute per 1.73 m2: No dosage adjustment necessary.70

eGFR <45 mL/minute per 1.73 m2: Do not initiate drug.70 Discontinue drug if eGFR is persistently <45 mL/minute per 1.73 m2.70

Empagliflozin/Metformin Hydrochloride Fixed-combination Therapy

eGFR ≥45 mL/minute per 1.73 m2: No dosage adjustment necessary for fixed combination containing empagliflozin and immediate - or extended-release metformin hydrochloride.72 74

eGFR <45 mL/minute per 1.73 m2: Contraindicated for fixed combination containing empagliflozin and immediate - or extended-release metformin hydrochloride.72 74

Geriatric Patients

Monotherapy

No dosage adjustment necessary based solely on age.1

Empagliflozin/Metformin Hydrochloride Fixed-combination Therapy

Monitor renal function frequently after initiating fixed-combination therapy.72 74

Cautions for Jardiance

Contraindications

  • History of serious hypersensitivity reaction to empagliflozin or any ingredient in the formulation.1

  • Severe renal impairment (eGFR <30 mL/minute per 1.73 m2), end-stage renal disease, or dialysis.1

Warnings/Precautions

Ketoacidosis

Ketoacidosis (e.g., diabetic ketoacidosis, ketoacidosis, ketosis) requiring hospitalization reported with SGLT2 inhibitors; may occur without markedly elevated blood glucose concentrations (e.g., <250 mg/dL).1 39 40 41 42 50

Evaluate for the presence of acidosis, including ketoacidosis, in patients experiencing signs or symptoms of acidosis regardless of the patient's blood glucose concentration; discontinue SGLT2 inhibitor and initiate appropriate treatment to correct acidosis if confirmed.1 39 40 50 (See Advice to Patients.)

Prior to initiating empagliflozin therapy, consider factors that may predispose patients to ketoacidosis (e.g., pancreatic insulin deficiency, reduced caloric intake, alcohol abuse).1 50

Consider temporarily discontinuing SGLT2 inhibitor in patients with clinical situations known to predispose to ketoacidosis (e.g., prolonged fasting due to acute illness or surgery).1 50

Some clinicians suggest monitoring of urine and/or plasma ketone levels if patients feel unwell, regardless of ambient glucose concentrations.40 42

Hypotension

May cause intravascular volume contraction.1 Symptomatic hypotension can occur, particularly in patients with impaired renal function, geriatric patients, patients receiving diuretics, or patients with low systolic BP.1 (See Specific Drugs and Laboratory Tests under Interactions.) Assess and correct intravascular volume status prior to initiating empagliflozin in patients.1

Monitor patients for signs and symptoms of hypotension after initiating therapy; increase monitoring in clinical situations in which volume contraction is expected.1

Renal Effects

Causes intravascular volume contraction and can cause renal impairment.1 51

May increase Scr concentration and decrease eGFR; hypovolemic patients may be more susceptible.1 Renal function abnormalities can occur following initiation of therapy.1

Consider factors that may predispose patients to acute kidney injury, such as hypovolemia, chronic renal insufficiency, heart failure, concomitant medications (e.g., diuretics, ACE inhibitors, angiotensin II receptor antagonists, NSAIAs), prior to initiating empagliflozin therapy.1 51

Consider temporarily discontinuing empagliflozin in any setting of reduced oral intake (e.g., acute illness, fasting) or fluid losses (e.g., GI illness, excessive heat exposure).1 51

Monitor patients for acute kidney injury; monitor patients with an eGFR <60 mL/minute per 1.73 m2 more frequently.1 Discontinue empagliflozin and initiate appropriate therapy if such injury occurs.1 51

Concomitant Therapy with Hypoglycemic Agents

When adding empagliflozin to therapy with an insulin secretagogue (e.g., a sulfonylurea) or insulin, consider reducing dosage of the concomitant insulin secretagogue or insulin to reduce the risk of hypoglycemia.1

Fournier Gangrene

Fournier gangrene (necrotizing fasciitis of the perineum), a rare but serious or life-threatening bacterial infection requiring urgent surgical intervention, reported during postmarketing surveillance in men and women with type 2 diabetes mellitus receiving an SGLT2 inhibitor.1 59 60 61 62

Assess for necrotizing fasciitis in patients receiving empagliflozin who develop pain or tenderness, erythema, or swelling in the genital or perineal area, in addition to fever or malaise.1 60 Discontinue empagliflozin if Fournier gangrene suspected; initiate treatment with broad-spectrum antibiotics and perform surgical debridement if necessary.1 60 Monitor blood glucose concentrations closely; initiate alternative antidiabetic agents to maintain glycemic control.1 60

Genital Mycotic Infections

Possible increased risk of genital mycotic infections in males (e.g., balanitis, balanoposthitis) and females (e.g., vulvovaginitis).1 Patients with a history of chronic or recurrent genital mycotic infections more likely to develop such infections.1 Genital mycotic infections also occurred more frequently in female than in male patients.1

Monitor patients for genital mycotic infections and institute appropriate treatment if these infections occur.1

Urosepsis and Pyelonephritis

May increase the risk of serious urinary tract infections (e.g., urosepsis, pyelonephritis requiring hospitalization).1 50 Patients with a history of chronic or recurrent urinary tract infections more likely to develop such infections.1

Urinary tract infections also occurred more frequently in female than in male patients, and risk of urinary tract infections increased in patients ≥75 years of age.1 Prior to initiating empagliflozin therapy, consider patient factors that may predispose to serious urinary tract infections (e.g., history of difficulty urinating; infection of the bladder, kidneys, or urinary tract).50

Monitor patients for urinary tract infections and initiate treatment if indicated.1

Effects on Lipoproteins

Dose-related increases in LDL-cholesterol concentration can occur.1 Monitor serum LDL-cholesterol concentrations and treat such lipid elevations according to standard of care.1

Potential Risk of Bone Fracture

Increased risk of bone fracture, along with dose-related decreases in bone mineral density in older adults, observed in patients receiving another SGLT2 inhibitor (canagliflozin).43 FDA continuing to evaluate bone fracture risk with SGLT2 inhibitors.43

Sensitivity Reactions

Serious hypersensitivity reactions (e.g., angioedema, urticaria) reported.1 Discontinue drug if hypersensitivity reaction occurs, institute appropriate treatment, and monitor patients until signs and symptoms resolve.1

Use of Fixed Combinations

When empagliflozin is used in fixed combination with metformin hydrochloride, linagliptin, or other drugs, consider the cautions, precautions, contraindications, and interactions associated with the concomitant agent(s) in addition to those associated with empagliflozin.1 70 72 74

Specific Populations

Pregnancy

No adequate and well-controlled studies using empagliflozin in pregnant women.1

Studies in animals indicate that empagliflozin use during pregnancy may affect renal development and maturation.1

Not recommended for use in the second or third trimesters of pregnancy.1

Lactation

Distributed into milk in rats; not known whether distributed into human milk.1 Discontinue nursing or the drug.1

Pediatric Use

Safety and efficacy not established in pediatric patients <18 years of age.1

Geriatric Use

Geriatric patients with renal impairment expected to experience reduced efficacy.1

Risk of volume depletion-related adverse effects and urinary tract infections increased in patients ≥75 years of age.1

Hepatic Impairment

No dosage adjustment necessary for patients with mild, moderate, or severe hepatic impairment.13

Renal Impairment

Glucose-lowering effect of empagliflozin 25 mg was reduced in patients with worsening renal function in a clinical study.1 9 In addition, risk of renal impairment and of volume depletion-related and urinary tract infection-related adverse effects increased with worsening renal function.1

Efficacy and safety not established in patients with severe renal impairment, end-stage renal disease, or in those receiving dialysis; empagliflozin is not expected to be effective in these patients and is contraindicated in such patients.1

Do not initiate drug in patients with eGFR <45 mL/minute per 1.73 m2.1 Discontinue drug if eGFR is persistently <45 mL/minute per 1.73 m2.1

Assess renal function before initiating empagliflozin and during therapy.1 More frequent monitoring recommended in patients with eGFR <60 mL/minute per 1.73 m2.1

Common Adverse Effects

Empagliflozin: Urinary tract infection,1 2 4 5 7 8 9 female genital mycotic infections,1 upper respiratory tract infection,1 4 5 increased urination,1 dyslipidemia,1 arthralgia,1 male genital mycotic infections,1 and nausea.1

Empagliflozin and linagliptin therapy: Urinary tract infection,70 nasopharyngitis,70 upper respiratory tract infection.70

Empagliflozin, metformin, and sulfonylurea combination therapy: Hypoglycemia,72 urinary tract infection,72 nasopharyngitis.72

Interactions for Jardiance

Metabolized principally by glucuronidation via uridine diphosphate-glucuronosyltransferase (UGT) isoenzymes 2B7, 1A3, 1A8, and 1A9.1

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Did not inhibit, inactivate, or induce CYP isoforms in vitro;1 no effect of empagliflozin expected on concomitantly administered drugs that are substrates of the major CYP isoforms.1

Drugs Affecting or Affected by Organic Anion Transporters

Substrate of organic anion transporter (OAT) 3 and organic anion transport proteins (OATP) 1B1 and 1B3.1 Not a substrate of OAT1.1 Does not inhibit any of these transporters at clinically relevant plasma concentrations; no effect of empagliflozin expected on concomitantly administered drugs that are substrates of these transporters.1

Drugs Affecting or Affected by Organic Cation Transporters

Not a substrate of organic cation transporter (OCT)2; does not inhibit OCT2 at clinically relevant plasma concentrations.1 No effect of empagliflozin expected on concomitantly administered drugs that are substrates of this transporter.1

Drugs Affecting or Metabolized by Uridine Diphosphate-glucuronosyltransferase

Does not inhibit UGT1A1, 1A3, 1A8, 1A9, or 2B7; no effect of empagliflozin expected on concomitantly administered drugs that are substrates of these UGT isoenzymes.1 Manufacturer states effect of UGT induction on empagliflozin exposure has not been studied.1

Drugs Affecting or Affected by P-glycoprotein Transport

Substrate of P-glycoprotein (P-gp); does not inhibit P-gp at therapeutic doses.1 Considered unlikely to cause interactions with drugs that are P-gp substrates based on in vitro studies.1

Drugs Affecting or Affected by Breast Cancer Resistance Protein

Substrate of breast cancer resistance protein (BCRP); does not inhibit BCRP at therapeutic doses.1

Specific Drugs and Laboratory Tests

Drug or Test

Interaction

Comments

Antidiabetic agents

Increased risk of hypoglycemia when used concomitantly with insulin or insulin secretagogues (e.g., sulfonylurea)1

Reduced dosage of insulin or insulin secretagogue may be required to reduce risk of hypoglycemia1

Digoxin

No clinically relevant effect on digoxin pharmacokinetics1

No adjustment of digoxin dosage necessary10

Diuretics

Concomitant use may increase urine volume and frequency of voids, which may increase risk of volume depletion1

Assess for volume contraction and correct prior to initiating empagliflozin;1 monitor for manifestations of hypotension after initiating therapy; increase monitoring in situations in which volume contraction expected1

Gemfibrozil

Increased empagliflozin AUC; however, effect not clinically relevant1

No adjustment of empagliflozin dosage necessary1

Glimepiride

No clinically relevant effect on pharmacokinetics of glimepiride or empagliflozin1 10

No adjustment of either drug dosage necessary10

Hormonal contraceptives

No clinically relevant effect on pharmacokinetics of ethinyl estradiol or levonorgestrel1

No adjustment of ethinyl estradiol or levonorgestrel dosage necessary10

Hydrochlorothiazide

No clinically relevant effect on pharmacokinetics of hydrochlorothiazide or empagliflozin1 10

No adjustment of either drug dosage necessary10

Linagliptin

No clinically relevant effect on pharmacokinetics of linagliptin or empagliflozin1 10

No adjustment of either drug dosage necessary10

Metformin

No clinically relevant effect on pharmacokinetics of metformin or empagliflozin1 10

No adjustment of either drug dosage necessary10

Pioglitazone

No clinically relevant effect on pharmacokinetics of empagliflozin or pioglitazone1

No adjustment of empagliflozin dosage necessary1

Probenecid

Increased empagliflozin AUC; however, effect not clinically relevant1

Concomitant use decreased fraction of empagliflozin excreted in urine by 30% without affecting 24-hour urinary glucose excretion in patients with normal renal function1

No adjustment of empagliflozin dosage necessary1

Ramipril

No clinically relevant effect on pharmacokinetics of ramipril, ramiprilat (metabolite), or empagliflozin1 10

No adjustment of ramipril or empagliflozin dosage necessary10

Rifampin

Increased empagliflozin AUC; however, effect not clinically relevant1

No adjustment of empagliflozin dosage necessary1

Simvastatin

No clinically relevant effect on pharmacokinetics of simvastatin, simvastatin acid (metabolite), or empagliflozin1 10

No adjustment of either drug dosage necessary10

Sitagliptin

No clinically relevant effect on pharmacokinetics of sitagliptin or empagliflozin1 10

No adjustment of either drug dosage necessary10

Torsemide

No clinically relevant effect on pharmacokinetics of torsemide or empagliflozin1 10

No adjustment of either drug dosage necessary10

Urine glucose tests (e.g., 1,5-anhydroglucitol assay)

SGLT2 inhibitors increase urinary glucose excretion and will result in false-positive urine glucose tests1

Use alternative methods to monitor glycemic control1

Verapamil

No clinically relevant effect on pharmacokinetics of empagliflozin1 10

No adjustment of verapamil dosage necessary10

Warfarin

No clinically relevant effect on pharmacokinetics of warfarin or empagliflozin1 10

No adjustment of either drug dosage necessary10

Jardiance Pharmacokinetics

Absorption

Bioavailability

Peak plasma concentration usually attained within 1 hour after oral dosing in fasted state.13 Empagliflozin exposure increases in proportion to the dose.1 13

Bioequivalence studies: Fixed-combination tablets of empagliflozin and immediate-release metformin hydrochloride or empagliflozin and linagliptin are bioequivalent to individual tablets of empagliflozin, metformin hydrochloride, or linagliptin administered concomitantly in equivalent doses.70 72

Food

Administration with a high-fat and high-calorie meal decreased peak concentration and AUC by approximately 37 and 16%, respectively, compared with fasting condition.1 These changes not considered clinically relevant; administer empagliflozin with or without food.1

Special Populations

Mild hepatic impairment (Child-Pugh class A): AUC and peak plasma concentration increased by 23 and 4%, respectively, compared with that in individuals with normal hepatic function.1 13

Moderate hepatic impairment (Child-Pugh class B): AUC and peak plasma concentration increased by 47 and 23%, respectively, compared with that in individuals with normal hepatic function.1 13

Severe hepatic impairment (Child-Pugh class C): AUC and peak plasma concentration increased by 75 and 48%, respectively, compared with that in individuals with normal hepatic function.1 13

Mild renal impairment (eGFR 60 to <90 mL/minute per 1.73 m2): AUC and peak plasma concentration increased by approximately 18 and 20%, respectively, compared with that in individuals with normal renal function.1

Moderate renal impairment (eGFR 30 to <60 mL/minute per 1.73 m2): AUC increased by 20% and peak plasma concentrations were similar compared with that in individuals with normal renal function.1

Severe renal impairment (eGFR <30 mL/minute per 1.73 m2): AUC and peak plasma concentration increased by approximately 66 and 20%, respectively, compared with that in individuals with normal renal function.1

Patients with renal failure/end-stage renal disease: AUC increased by approximately 48% and peak plasma concentrations were similar compared with that in individuals with normal renal function.1

Distribution

Plasma Protein Binding

86.2%1

Elimination

Metabolism

Metabolized principally via glucuronidation by UGT isoenzymes 2B7, 1A3, 1A8, and 1A9.1

Elimination Route

Following administration of radiolabeled dose of empagliflozin, eliminated in feces (41.2%) and urine (54.4%).1

Half-life

Approximately 12.4 hours1

Special Populations

Apparent oral clearance of empagliflozin decreases with a reduction in eGFR.1 Fraction of empagliflozin excreted unchanged in urine and urinary glucose excretion decline with decrease in eGFR.1

Gender, race, and body weight have no clinically meaningful effect on pharmacokinetics of empagliflozin.1

Stability

Storage

Oral

Tablets

Empagliflozin, fixed combination of empagliflozin and linagliptin, and fixed combination of empagliflozin and metformin hydrochloride: 25°C (may be exposed to 15–30°C).1 70 72 74

Actions

  • Inhibits SGLT2, the transporter principally responsible for reabsorption of glucose from the glomerular filtrate back into the circulation.1 11 12

  • Reduces renal reabsorption of filtered glucose and lowers the renal threshold for glucose, thereby increasing urinary glucose excretion.1 11 12

  • Increases glucose excretion independent of insulin secretion.1 11 12

  • Reduces blood glucose concentrations.1 11 12

Advice to Patients

  • When empagliflozin is used in fixed combination with other drugs, importance of informing patients of important cautionary information about the concomitant agent(s).1 70 72 74

  • Importance of patient reading medication guide before initiating therapy and each time the drug is dispensed.1 14 70 71 72 73 74 75

  • Importance of informing patients of the potential risks and benefits of empagliflozin and of alternative therapies.1 Importance of informing patients that use of empagliflozin with other antidiabetic agents may increase risk of hypoglycemia.1 14 Importance of not using empagliflozin in patients with type 1 diabetes mellitus or diabetic ketoacidosis.1

  • Importance of informing patients that ketoacidosis, which can be a life-threatening condition, has been reported with empagliflozin therapy.1 14 Importance of informing patients and their caregivers of the signs and symptoms of ketoacidosis (e.g., tachypnea or hyperventilation, anorexia, abdominal pain, nausea, vomiting, lethargy, mental status changes) and of instructing patients to discontinue empagliflozin and seek medical attention immediately should they experience any such signs or symptoms.1 14 39 42 50 Advise patients to use a ketone dipstick to check for ketones in their urine (when possible) if symptoms of ketoacidosis occur, even if blood glucose is not elevated (e.g., <250 mg/dL).1 14 50

  • Importance of informing patients that hypotension may occur with empagliflozin and to report such symptoms to their clinicians.1 14 Inform patients that empagliflozin-induced dehydration may increase the risk of hypotension and that patients should maintain adequate fluid intake.1 14

  • Importance of informing patients that acute kidney injury has been reported with empagliflozin therapy.1 Advise patients to seek medical advice immediately if they have reduced oral intake (such as due to acute illness or fasting) or increased fluid losses (such as due to vomiting, diarrhea, or excessive heat exposure), as it may be appropriate to temporarily discontinue empagliflozin in those situations.1

  • Importance of informing female patients that vaginal yeast infections may occur (e.g., vulvovaginitis).1 14 Importance of informing male patients that yeast infections may occur (e.g., balanitis, balanoposthitis), especially in uncircumcised males.1 14 Importance of informing patients that yeast infections occur more frequently in females and in patients with chronic and recurrent infections.1 Importance of informing female patients of the signs and symptoms of vaginal yeast infections (e.g., vaginal discharge, odor, itching) and male patients of the signs and symptoms of balanitis or balanoposthitis (e.g. rash or redness of the glans or foreskin of the penis, foul-smelling discharge from the penis, pain in skin around penis).1 14 Advise patients of treatment options and when to seek medical advice.1

  • Importance of informing patients of the potential for urinary tract infections, which may be serious, with empagliflozin therapy.1 14 50 Advise patients of the signs and symptoms of urinary tract infections (e.g. dysuria, cloudy urine, pelvic or back pain) and the need to report such symptoms to their clinicians.1 14

  • Importance of informing patients that necrotizing infections of the perineum (Fournier gangrene) have occurred with empagliflozin therapy.1 60 Advise patients to seek prompt medical attention if they experience any symptoms of tenderness, redness, or swelling of the genitals or the area from the genitals back to the rectum, occurring with a fever above 38°C or malaise.1 60

  • Risk of serious hypersensitivity reactions, such as urticaria and angioedema.1 If signs or symptoms of such reactions occur, importance of discontinuing empagliflozin and informing clinician promptly.1

  • Importance of informing patients that due to the mechanism of action of empagliflozin, patients taking the drug will test positive for glucose in the urine.1 14 Importance of not using urine glucose tests to monitor glycemic status while taking empagliflozin.1

  • Importance of informing patients about the importance of adherence to dietary instructions, regular physical activity, periodic blood glucose monitoring and glycosylated hemoglobin (hemoglobin A1c; HbA1c) testing, recognition and management of hypoglycemia and hyperglycemia, and assessment of diabetes complications.1 14

  • Importance of seeking medical advice promptly during periods of stress such as fever, trauma, infection, or surgery as dosage requirements may change.1 14

  • Importance of informing patient not to take empagliflozin if allergic to the drug or any ingredients in the formulation.1 14

  • Importance of taking empagliflozin exactly as directed by clinician.14 Importance of informing patients that if a dose is missed, it should be taken as soon as remembered; the dose should not be doubled to make up for the missed dose.1 14 (See Dosage and Administration: Administration.)

  • Importance of informing patients that renal function should be assessed prior to initiation of empagliflozin and monitored periodically thereafter.1

  • Importance of women informing their clinicians if they are or plan to become pregnant or plan to breast-feed.1 14

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.1 14

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Empagliflozin

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

10 mg

Jardiance

Boehringer Ingelheim

25 mg

Jardiance

Boehringer Ingelheim

Empagliflozin Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, extended-release

5 mg with Extended-release Metformin Hydrochloride 1 g

Synjardy XR

Boehringer Ingelheim

10 mg with Extended-release Metformin Hydrochloride 1 g

Synjardy XR

Boehringer Ingelheim

12.5 mg with Extended-release Metformin Hydrochloride 1 g

Synjardy XR

Boehringer Ingelheim

25 mg with Extended-release Metformin Hydrochloride 1 g

Synjardy XR

Boehringer Ingelheim

Tablets, film-coated

5 mg with Metformin Hydrochloride 500 mg

Synjardy

Boehringer Ingelheim

5 mg with Metformin Hydrochloride 1 g

Synjardy

Boehringer Ingelheim

10 mg with Linagliptin 5 mg

Glyxambi

Boehringer Ingelheim

12.5 mg with Metformin Hydrochloride 500 mg

Synjardy

Boehringer Ingelheim

12.5 mg with Metformin Hydrochloride 1 g

Synjardy

Boehringer Ingelheim

25 mg with Linagliptin 5 mg

Glyxambi

Boehringer Ingelheim

AHFS DI Essentials™. © Copyright 2020, Selected Revisions November 18, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

References

1. Boehringer Ingelheim Pharmaceuticals, Inc. Jardiance (empagliflozin) tablets prescribing information. Ridgefield, CT; 2018 Oct.

2. Roden M, Weng J, Eilbracht J et al. Empagliflozin monotherapy with sitagliptin as an active comparator in patients with type 2 diabetes: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Diabetes Endocrinol. 2013; 1:208-19. http://www.ncbi.nlm.nih.gov/pubmed/24622369?dopt=AbstractPlus

3. Häring HU, Merker L, Seewaldt-Becker E et al. Empagliflozin as add-on to metformin in patients with type 2 diabetes: a 24-week, randomized, double-blind, placebo-controlled trial. Diabetes Care. 2014; 37:1650-9. http://www.ncbi.nlm.nih.gov/pubmed/24722494?dopt=AbstractPlus

4. Häring HU, Merker L, Seewaldt-Becker E et al. Empagliflozin as add-on to metformin plus sulfonylurea in patients with type 2 diabetes: a 24-week, randomized, double-blind, placebo-controlled trial. Diabetes Care. 2013; 36:3396-404. http://www.ncbi.nlm.nih.gov/pubmed/23963895?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=3816918&blobtype=pdf

5. Ridderstråle M, Andersen KR, Zeller C et al. Comparison of empagliflozin and glimepiride as add-on to metformin in patients with type 2 diabetes: a 104-week randomised, active-controlled, double-blind, phase 3 trial. Lancet Diabetes Endocrinol. 2014; 2:691-700. http://www.ncbi.nlm.nih.gov/pubmed/24948511?dopt=AbstractPlus

6. Ridderstråle M, Svaerd R, Zeller C et al. Rationale, design and baseline characteristics of a 4-year (208-week) phase III trial of empagliflozin, an SGLT2 inhibitor, versus glimepiride as add-on to metformin in patients with type 2 diabetes mellitus with insufficient glycemic control. Cardiovasc Diabetol. 2013; 12:129. http://www.ncbi.nlm.nih.gov/pubmed/24007456?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=3844307&blobtype=pdf

7. Kovacs CS, Seshiah V, Swallow R et al. Empagliflozin improves glycaemic and weight control as add-on therapy to pioglitazone or pioglitazone plus metformin in patients with type 2 diabetes: a 24-week, randomized, placebo-controlled trial. Diabetes Obes Metab. 2014; 16:147-58. http://www.ncbi.nlm.nih.gov/pubmed/23906415?dopt=AbstractPlus

8. Rosenstock J, Jelaska A, Frappin G et al. Improved glucose control with weight loss, lower insulin doses, and no increased hypoglycemia with empagliflozin added to titrated multiple daily injections of insulin in obese inadequately controlled type 2 diabetes. Diabetes Care. 2014; 37:1815-23. http://www.ncbi.nlm.nih.gov/pubmed/24929430?dopt=AbstractPlus

9. Barnett AH, Mithal A, Manassie J et al. Efficacy and safety of empagliflozin added to existing antidiabetes treatment in patients with type 2 diabetes and chronic kidney disease: a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2014; 2:369-84. http://www.ncbi.nlm.nih.gov/pubmed/24795251?dopt=AbstractPlus

10. Scheen AJ. Pharmacokinetic and pharmacodynamic profile of empagliflozin, a sodium glucose co-transporter 2 inhibitor. Clin Pharmacokinet. 2014; 53:213-25. http://www.ncbi.nlm.nih.gov/pubmed/24430725?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=3927118&blobtype=pdf

11. . Empagliflozin (Jardiance) for diabetes. Med Lett Drugs Ther. 2014; 56:99-100. http://www.ncbi.nlm.nih.gov/pubmed/25296258?dopt=AbstractPlus

12. Jahagirdar V, Barnett AH. Empagliflozin for the treatment of type 2 diabetes. Expert Opin Pharmacother. 2014; 15:2429-41. http://www.ncbi.nlm.nih.gov/pubmed/25301180?dopt=AbstractPlus

13. US Food and Drug Administration. Center for Drug Evaluation and Research. Application number 204629Orig1s000: Clinical Pharmacology and Biopharmaceutics Review(s). From FDA website. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204629Orig1s000ClinPharmR.pdf

14. Boehringer Ingelheim Pharmaceuticals, Inc. Jardiance (empagliflozin) tablets medication guide. 2018 Oct.

39. US Food and Drug Administration. FDA Drug Safety Communication: FDA warns that SGLT2 inhibitors for diabetes may result in a serious condition of too much acid in the blood. From FDA website. Accessed 2015 July 6. http://www.fda.gov/downloads/Drugs/DrugSafety/UCM446954.pdf

40. Rosenstock J, Ferrannini E. Euglycemic diabetic ketoacidosis: a predictable, detectable, and preventable safety concern with SGLT2 inhibitors. Diabetes Care. 2015; 38:1638-42. http://www.ncbi.nlm.nih.gov/pubmed/26294774?dopt=AbstractPlus

41. Erondu N, Desai M, Ways K et al. Diabetic ketoacidosis and related events in the canagliflozin type 2 diabetes clinical program. Diabetes Care. 2015; 38:1680-6. http://www.ncbi.nlm.nih.gov/pubmed/26203064?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=4542268&blobtype=pdf

42. Peters AL, Buschur EO, Buse JB et al. Euglycemic diabetic ketoacidosis: a potential complication of treatment with sodium-glucose cotransporter 2 inhibition. Diabetes Care. 2015; 38:1687-93. http://www.ncbi.nlm.nih.gov/pubmed/26078479?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=4542270&blobtype=pdf

43. US Food and Drug Administration. FDA Drug Safety Communication: FDA revises label of diabetes drug canagliflozin (Invokana, Invokamet) to include updates on bone fracture risk and new information on decreased bone mineral density. 2015 Sep 10. From FDA website. Accessed 2015 Sep 13. http://www.fda.gov/Drugs/DrugSafety/ucm461449.htm

44. DeFronzo RA, Lewin A, Patel S et al. Combination of empagliflozin and linagliptin as second-line therapy in subjects with type 2 diabetes inadequately controlled on metformin. Diab Care. 2015 Mar; 38:384-93.

50. US Food and Drug Administration. FDA Drug Safety Communication: FDA revises labels of SGLT2 inhibitors for diabetes to include warnings about too much acid in the blood and serious urinary tract infections. From FDA website. http://www.fda.gov/downloads/Drugs/DrugSafety/UCM475487.pdf

51. US Food and Drug Administration. FDA Drug Safety Communication: FDA strengthens kidney warnings for diabetes medicine canagliflozin (Invokana, Invokamet) and dapagliflozin (Farxiga, Xigduo XR). From FDA website. http://www.fda.gov/downloads/Drugs/DrugSafety/UCM506772.pdf

54. Janssen Pharmaceuticals, Inc. Invokana (canagliflozin) tablets prescribing information. Titusville, NJ; 2016 May.

55. Bristol-Myers Squibb Company. Farxiga (dapagliflozin) tablets prescribing information. Princeton, NJ; 2016 Jun.

59. Bersoff-Matcha SJ, Chamberlain C, Cao C et al. Fournier gangrene associated with sodium-glucose cotransporter-2 inhibitors: a review of spontaneous postmarketing cases. Ann Intern Med. 2019; 170:764-9. http://www.ncbi.nlm.nih.gov/pubmed/31060053?dopt=AbstractPlus

60. US Food and Drug Administration. FDA Drug Safety Communication: FDA warns about rare occurrences of a serious infection of the genital area with SGLT2 inhibitors for diabetes. Silver Spring, MD; 2018 Aug 29. From FDA website. https://www.fda.gov/downloads/Drugs/DrugSafety/UCM618466.pdf

61. Cecilia-Chi W, Lim-Tio S. Fournier's syndrome: a life-threatening complication of SGLT2 inhibition in poorly controlled diabetes mellitus. 2016 Joint Annual Scientific Meeting of the Australian Diabetes Educators Association (ADEA) and Australian Diabetes Society (ADS). Abstract number 265.

62. Kumar S, Costello AJ, Colman PG. Fournier's gangrene in a man on empagliflozin for treatment of Type 2 diabetes. Diabet Med. 2017; 34:1646-1648. http://www.ncbi.nlm.nih.gov/pubmed/28887847?dopt=AbstractPlus

70. Boehringer Ingelheim Pharmaceuticals, Inc. Glyxambi (empagliflozin and linagliptin) tablets prescribing information. Ridgefield, CT; 2019 Jul.

71. Boehringer Ingelheim Pharmaceuticals, Inc. Glyxambi (empagliflozin and linagliptin) tablets medication guide. Ridgefield, CT; 2019 Jult.

72. Boehringer Ingelheim Pharmaceuticals, Inc. Synjardy (empagliflozin and metformin hydrochloride) tablets prescribing information. Ridgefield, CT; 2018 Oct.

73. Boehringer Ingelheim Pharmaceuticals, Inc. Synjardy (empagliflozin and metformin hydrochloride) medication guide. Ridgefield, CT; 2018 Oct.

74. Boehringer Ingelheim Pharmaceuticals, Inc. Synjardy XR (empagliflozin and metformin hydrochloride extended-release) tablets prescribing information. Ridgefield, CT; 2018 Oct.

75. Boehringer Ingelheim Pharmaceuticals, Inc. Synjardy XR (empagliflozin and metformin hydrochloride extended-release) medication guide. Ridgefield, CT; 2018 Oct.

84. Trujillo JM, Nuffer WA. Impact of Sodium-Glucose Cotransporter 2 Inhibitors on Nonglycemic Outcomes in Patients with Type 2 Diabetes. Pharmacotherapy. 2017; 37:481-491. http://www.ncbi.nlm.nih.gov/pubmed/28102030?dopt=AbstractPlus

85. Inzucchi SE, Zinman B, Wanner C et al. SGLT-2 inhibitors and cardiovascular risk: proposed pathways and review of ongoing outcome trials. Diab Vasc Dis Res. 2015; 12:90-100. http://www.ncbi.nlm.nih.gov/pubmed/25589482?dopt=AbstractPlus

90. Zinman B, Wanner C, Lachin JM et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015; 373:2117-28. http://www.ncbi.nlm.nih.gov/pubmed/26378978?dopt=AbstractPlus

91. Wanner C, Inzucchi SE, Lachin JM et al. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med. 2016; 375:323-34. http://www.ncbi.nlm.nih.gov/pubmed/27299675?dopt=AbstractPlus

598. Garber AJ, Abrahamson MJ, Barzilay JI et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endorinology on the comprehensive type 2 diabetes management algorithm - 2019 executive summary. Endocr Pract. 2019; 25:69-100. http://www.ncbi.nlm.nih.gov/pubmed/30742570?dopt=AbstractPlus

604. American Diabetes Association. 9. Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes-2019. Diabetes Care. 2019; 42:S90-S102. http://www.ncbi.nlm.nih.gov/pubmed/30559235?dopt=AbstractPlus

605. American Diabetes Association. 10. Cardiovascular disease and risk management: standards of medical care in diabetes-2019. Diabetes Care. 2019; 42:S103-S123. http://www.ncbi.nlm.nih.gov/pubmed/30559236?dopt=AbstractPlus

606. American Diabetes Association. 11. Microvascular complications and foot care: standards of medical care in diabetes-2019. Diabetes Care. 2019; 42:S124-S138. http://www.ncbi.nlm.nih.gov/pubmed/30559237?dopt=AbstractPlus

Related questions