Jardiance - Drug Monograph

Introduction

Jardiance (empagliflozin) is an oral antihyperglycemic agent belonging to the sodium-glucose cotransporter 2 (SGLT2) inhibitor class. Approved by the FDA in 2014, it represents a significant advancement in diabetes management with additional benefits for cardiovascular and renal protection.

Mechanism of Action

Empagliflozin inhibits sodium-glucose cotransporter 2 (SGLT2) in the proximal renal tubules. This inhibition reduces renal glucose reabsorption, increases urinary glucose excretion, and lowers blood glucose concentrations. Unlike many other diabetes medications, Jardiance's mechanism is insulin-independent.

Indications

• Type 2 Diabetes Mellitus: As an adjunct to diet and exercise to improve glycemic control
• Cardiovascular Risk Reduction: To reduce the risk of cardiovascular death in adults with type 2 diabetes and established cardiovascular disease
• Heart Failure: To reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure
• Chronic Kidney Disease: To reduce the risk of sustained eGFR decline, end-stage kidney disease, cardiovascular death, and hospitalization in adults with chronic kidney disease

Dosage and Administration

• Initial dose: 10 mg once daily in the morning
• May increase to: 25 mg once daily if tolerated
• Administration: Taken with or without food
• Renal impairment: Not recommended when eGFR <30 mL/min/1.73m²; discontinue when eGFR falls persistently below 30 mL/min/1.73m²
• Hepatic impairment: No dosage adjustment necessary
• Elderly: No dosage adjustment required based on age alone

Pharmacokinetics

• Absorption: Rapid with peak plasma concentrations achieved in 1.5 hours
• Bioavailability: ~78%
• Distribution: Extensive protein binding (~86%)
• Metabolism: Primarily via glucuronidation by UGT1A3, UGT1A8, UGT1A9, and UGT2B7
• Elimination: Half-life ~12 hours; primarily eliminated via feces (41.2%) and urine (54.4%)
• Clearance: Renal and hepatic pathways

Contraindications

• History of serious hypersensitivity to empagliflozin or any product components
• Severe renal impairment (eGFR <30 mL/min/1.73m²), end-stage renal disease, or dialysis
• Concomitant use with other SGLT2 inhibitors

Warnings and Precautions

• Ketoacidosis: Reports of life-threatening ketoacidosis requiring hospitalization
• Volume Depletion: May cause symptomatic hypotension; assess volume status before initiation
• UTIs: Increased risk of urinary tract infections
• Genital Mycotic Infections: Higher incidence of fungal infections
• Hypoglycemia: Risk increased when used with insulin or insulin secretagogues
• Necrotizing Fasciitis: Rare but serious infections of the perineum (Fournier's gangrene)
• Lower Limb Amputation: Increased risk observed in clinical trials

Drug Interactions

• Diuretics: Increased risk of volume depletion
• Insulin/Insulin Secretagogues: Increased risk of hypoglycemia
• UGT Inducers: Rifampin may decrease empagliflozin concentrations
• Lithium: SGLT2 inhibitors may decrease lithium concentrations

Adverse Effects

• Urinary tract infections
• Female genital mycotic infections
• Increased urination
• Upper respiratory tract infections

• Ketoacidosis
• Acute kidney injury
• Urosepsis and pyelonephritis
• Hypersensitivity reactions
• Fournier's gangrene
• Bone fractures
• Lower limb amputations

Monitoring Parameters

• Glycemic control: HbA1c every 3-6 months
• Renal function: Serum creatinine/eGFR at initiation and periodically
• Volume status: Blood pressure, signs/symptoms of hypotension
• Ketones: During periods of stress, illness, or when symptoms suggest ketoacidosis
• Genital hygiene and symptoms: For mycotic infections
• Foot exams: Regular examination for lesions, ulcers, or infections
• Lipid profile: Periodically

Patient Education

• Take medication as prescribed, typically once daily in the morning
• Maintain adequate hydration to prevent volume depletion
• Recognize symptoms of hypoglycemia (shaking, sweating, confusion)
• Report symptoms of urinary tract or genital infections promptly
• Monitor for signs of ketoacidosis (nausea, vomiting, abdominal pain, fatigue)
• Practice regular foot care and inspection
• Continue diet and exercise recommendations
• Inform all healthcare providers about Jardiance use, especially before surgical procedures
• Understand potential side effects and when to seek medical attention

References

1. FDA Prescribing Information: Jardiance (empagliflozin) tablets 2. Zinman B, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015;373(22):2117-2128 3. Wanner C, et al. Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes. N Engl J Med. 2016;375(4):323-334 4. Packer M, et al. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. N Engl J Med. 2020;383(15):1413-1424 5. American Diabetes Association. Standards of Medical Care in Diabetes—2023. Diabetes Care. 2023;46(Suppl 1):S1-S291