Usage
Empagliflozin is prescribed as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (T2DM). It is also indicated to reduce the risk of cardiovascular death in adults with T2DM and established cardiovascular disease, and to reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure (HF). Additionally, it is used to reduce the risk of sustained decline in estimated glomerular filtration rate (eGFR), end-stage kidney disease, cardiovascular death, and hospitalization in adults with chronic kidney disease (CKD) at risk of progression.
It is classified as a sodium-glucose co-transporter 2 (SGLT2) inhibitor.
Empagliflozin works by inhibiting SGLT2 in the kidneys. This blocks the reabsorption of glucose from the glomerular filtrate back into the bloodstream, increasing urinary glucose excretion and lowering blood glucose levels.
Alternate Names
The international nonproprietary name (INN) is empagliflozin. A common brand name is Jardiance. Other brand names include Synjardy (empagliflozin/metformin) and Glyxambi (empagliflozin/linagliptin).
How It Works
Pharmacodynamics: Empagliflozin lowers blood glucose levels by increasing urinary glucose excretion. It also may have beneficial effects on blood pressure and body weight. In patients with heart failure, empagliflozin can help to reduce the risk of cardiovascular death and hospitalization. It can also slow down the progression of kidney failure in patients with chronic kidney disease.
Pharmacokinetics:
- Absorption: Empagliflozin is rapidly absorbed after oral administration.
- Metabolism: It is primarily metabolized via glucuronidation.
- Elimination: Primarily eliminated through urine (41.2%) and feces (41.1%), with a small portion through metabolism (17.8%). The elimination half-life is approximately 12.4 hours.
Mode of Action: Empagliflozin selectively inhibits SGLT2 in the kidneys, preventing glucose reabsorption and promoting its excretion in urine. It does not directly affect insulin secretion or action.
Elimination Pathways: Primarily renal and fecal excretion.
Dosage
Standard Dosage
Adults:
- T2DM: 10 mg orally once daily in the morning. May increase to 25 mg once daily if needed and tolerated, based on renal function and glycemic control.
- Heart Failure: 10 mg orally once daily.
- CKD: 10 mg orally once daily.
Children (10 years and older):
- T2DM: 10 mg orally once daily in the morning. May increase to 25 mg once daily if needed and tolerated.
Special Cases:
- Elderly Patients: No specific dose adjustments are needed based solely on age, but consideration should be given to renal function and risk of volume depletion.
- Patients with Renal Impairment: In patients with an eGFR < 20 ml/min/1.73 m² or on dialysis for Heart Failure or CKD, the use of empagliflozin is not recommended due to a lack of studies in this patient population. For T2DM with eGFR < 30, the use of empagliflozin is not recommended.
- Patients with Hepatic Dysfunction: No dose adjustment is necessary for mild to moderate hepatic impairment. Not recommended for patients with severe hepatic impairment.
- Patients with Comorbid Conditions: Dosage adjustments may be needed in patients with multiple conditions. Consider lower doses of sulfonylureas or insulin when used in combination with empagliflozin to reduce the risk of hypoglycemia.
Clinical Use Cases
Empagliflozin is not typically used in the following clinical settings:
- Intubation
- Surgical Procedures: Withhold for at least 3 days before major surgery or procedures with prolonged fasting. Resume once the patient is clinically stable and has resumed oral intake.
- Mechanical Ventilation
- Intensive Care Unit (ICU) Use
- Emergency Situations
Dosage Adjustments
Dosage adjustments might be necessary based on patient-specific factors like renal/hepatic impairment, concurrent medications, and other comorbid conditions. Close monitoring is essential, especially when starting empagliflozin or changing doses.
Side Effects
Common Side Effects:
- Genital mycotic infections (e.g., vulvovaginal candidiasis)
- Urinary tract infections (UTIs)
- Increased urination
Rare but Serious Side Effects:
- Diabetic ketoacidosis (DKA), especially in patients with type 1 diabetes
- Necrotizing fasciitis of the perineum (Fournier’s gangrene)
- Acute kidney injury
- Hypotension and dehydration
Long-Term Effects:
- Increased risk of bone fractures
Adverse Drug Reactions (ADR):
- Angioedema
- Hypersensitivity reactions
Contraindications
- Hypersensitivity to empagliflozin
- Type 1 diabetes mellitus
- Diabetic ketoacidosis
- Severe renal impairment (eGFR <30 mL/min/1.73 m²) for T2DM
- End-stage renal disease or patients on dialysis for HF or CKD
- Severe hepatic impairment
Drug Interactions
Empagliflozin may interact with:
- Diuretics: Increased risk of dehydration and hypotension.
- Insulin and Sulfonylureas: Increased risk of hypoglycemia.
- Other Antihypertensive Medications: Enhanced hypotensive effects.
Pregnancy and Breastfeeding
- Pregnancy: Not recommended during pregnancy due to potential fetal risks.
- Breastfeeding: Not recommended while breastfeeding due to limited data on infant safety.
Drug Profile Summary
- Mechanism of Action: SGLT2 inhibitor, increases urinary glucose excretion.
- Side Effects: Genital infections, UTIs, increased urination, DKA (rare), hypotension.
- Contraindications: Hypersensitivity, type 1 diabetes, DKA, severe renal or hepatic impairment, dialysis.
- Drug Interactions: Diuretics, insulin, sulfonylureas, antihypertensives.
- Pregnancy & Breastfeeding: Not recommended.
- Dosage: Adults/Children (T2DM): 10-25 mg once daily; HF/CKD: 10 mg once daily.
- Monitoring Parameters: Blood glucose, HbA1c, renal function, blood pressure, electrolytes, ketones, signs of UTI and genital infections.
Popular Combinations
Precautions
- General Precautions: Assess renal function before and during treatment. Monitor for signs of DKA, UTIs, genital infections, volume depletion.
- Specific Populations: Not recommended for pregnant or breastfeeding women. Consider renal function and volume depletion risk in elderly patients. Not recommended for children under 10.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Empagliflozin?
A: The standard starting dose is 10 mg once daily, taken orally in the morning. The dose can be increased to 25 mg daily if needed and tolerated.
Q2: How does Empagliflozin differ from other diabetes medications?
A: Empagliflozin works by increasing urinary glucose excretion, independent of insulin secretion or action, unlike other classes like sulfonylureas or DPP-4 inhibitors.
Q3: What are the common side effects of Empagliflozin?
A: Common side effects include genital mycotic infections, UTIs, and increased urination.
Q4: Can Empagliflozin be used in patients with type 1 diabetes?
A: No, empagliflozin is contraindicated in patients with type 1 diabetes due to the risk of DKA.
Q5: What are the serious side effects of Empagliflozin to watch out for?
A: Serious but rare side effects include DKA, necrotizing fasciitis of the perineum (Fournier’s gangrene), and acute kidney injury.
Q6: Are there any drug interactions with Empagliflozin?
A: Yes, Empagliflozin can interact with diuretics, insulin, sulfonylureas, and other antihypertensive medications.
Q7: Can Empagliflozin be used during pregnancy or breastfeeding?
A: Empagliflozin is not recommended during pregnancy or breastfeeding.
Q8: What monitoring parameters are important for patients on Empagliflozin?
A: Monitor blood glucose, HbA1c, renal function, blood pressure, electrolytes, and signs of UTIs and genital infections.
Q9: When should Empagliflozin be temporarily discontinued?
A: Temporarily discontinue Empagliflozin at least 3 days before major surgery or procedures involving prolonged fasting, and during acute serious illnesses.
Q10: Is Empagliflozin safe for long-term use?
A: Empagliflozin is generally considered safe for long-term use, but patients should be monitored for potential side effects and complications.
