Brand name: Jardiance
Drug class: Sodium-glucose Cotransporter 2 (SGLT2) Inhibitors
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 on Dec 1, 2022. Written by ASHP.

Introduction

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

Uses for Empagliflozin

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 receptor_γ [PPAR_γ] 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 in patients with recent-onset type 2 diabetes mellitus or mild hyperglycemia because of its well-established safety and efficacy (i.e., beneficial effects on glycosylated hemoglobin [hemoglobin A_1c; HbA_1c], weight, and cardiovascular mortality).^{698 704 705}

In patients with metformin contraindications or intolerance (e.g., risk of lactic acidosis, GI intolerance) or in selected other patients, some experts suggest that initial therapy with a drug from another class of antidiabetic agents (e.g., a glucagon-like peptide 1 [GLP-1] receptor agonist, SGLT2 inhibitor, DPP-4 inhibitor, sulfonylurea, thiazolidinedione, basal insulin) may be acceptable based on patient factors.⁶⁹⁸

May need to initiate therapy with 2 agents (e.g., metformin plus another drug) in patients with high initial HbA_1c (>7.5% or ≥1.5% above target).^{698 704} In such patients with metformin intolerance, some experts suggest initiation of therapy with 2 drugs from other drug classes with complementary mechanisms of action.⁶⁹⁸

Consider early initiation of combination therapy for the treatment of type 2 diabetes mellitus to extend the time to treatment failure and more rapidly attain glycemic goals.⁷⁰⁴

For patients with inadequate glycemic control on metformin monotherapy, consider patient comorbidities (e.g., atherosclerotic cardiovascular disease [ASCVD], established kidney disease, heart failure), hypoglycemia risk, impact on weight, cost, risk of adverse effects, and patient preferences when selecting additional antidiabetic agents for combination therapy.^{698 704 705 706}

Consider early introduction of insulin for severe hyperglycemia (e.g., blood glucose of ≥300 mg/dL or HbA_1c >9–10%), especially if accompanied by catabolic manifestations (e.g., weight loss, hypertriglyceridemia, ketosis) or symptoms of hyperglycemia.^{698 704}

Experts recommend that patients with type 2 diabetes mellitus who have established (or are at a high risk for) ASCVD, established kidney disease, or heart failure receive a GLP-1 receptor agonist or SGLT2 inhibitor with demonstrated cardiovascular disease benefit.^{704 705} In patients with these comorbidities, consider GLP-1 receptor agonist or SGLT2 inhibitor therapy independently of patient's HbA_1c.⁷⁰⁴

In patients with type 2 diabetes mellitus and CKD, consider a GLP-1 receptor agonist or SGLT2 inhibitor shown to reduce the risk of CKD progression, cardiovascular events, or both, in addition to metformin therapy or in those in whom metformin cannot be used.^{704 705 706}

In patients on metformin monotherapy without established ASCVD or indicators of high ASCVD risk, heart failure, or CKD, base decision regarding addition of other antidiabetic agents on avoidance of adverse effects, cost, and individual patient factors.⁷⁰⁴

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

Beneficial Effects on Renal Function

Some experts suggest that SGLT2 inhibitor therapy be considered to reduce risk of CKD progression, cardiovascular events, or both in patients with type 2 diabetes mellitus and diabetic kidney disease with albuminuria^{† [off-label]} (eGFR ≥30 mL/minute per 1.73 m² and urinary albumin >30 mg/g [particularly >300 mg/g] creatinine).⁷⁰⁶

Empagliflozin 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

Recommended dosage is 10 mg once daily in the morning.¹

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

Empagliflozin/Linagliptin Fixed-combination Therapy

Oral

Recommended dosage is 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 in the morning.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 in the morning.⁷⁴

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

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 Empagliflozin

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 discontinuing empagliflozin for ≥3 days prior to surgery for patients with scheduled surgery.¹

Consider temporarily discontinuing SGLT2 inhibitor in patients with other clinical situations known to predispose to ketoacidosis (e.g., prolonged fasting due to acute illness or post-surgery).^{1 50} Risk factors for ketoacidosis should be resolved prior to restarting empagliflozin.¹

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 S_cr 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

Drug Interactions

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

Empagliflozin 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 (sometimes associated with illness or surgery among other risk factors).^{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 A_1c; HbA_1c) 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.

Frequently asked questions

• How long does it take for Jardiance to work?

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