Ajardy

Approved Indications:

• Type 2 Diabetes Mellitus (T2DM):
  Used as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus, either as monotherapy or in combination with other antidiabetic agents.
• Cardiovascular Risk Reduction:
  Indicated to reduce the risk of cardiovascular death in adults with type 2 diabetes mellitus and established cardiovascular disease.
• Heart Failure with Reduced Ejection Fraction (HFrEF):
  Approved to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with HFrEF, regardless of diabetes status.
• Chronic Kidney Disease (CKD):
  Indicated to slow the progression of kidney disease and reduce the risk of cardiovascular death and hospitalization in adults with CKD (with or without diabetes).

Important Off-Label (Clinically Accepted) Uses:

• Type 1 Diabetes Mellitus (T1DM):
  Though not FDA-approved, some endocrinologists may use Empagliflozin off-label in carefully selected type 1 diabetes patients with close monitoring to improve glycemic control, while managing the risk of ketoacidosis.

Adults:

• T2DM & Cardiovascular Risk Reduction:
• Initial dose: 10 mg orally once daily in the morning, with or without food.
• May increase to 25 mg once daily if additional glycemic control is needed.
• Heart Failure (HFrEF):
• 10 mg orally once daily, with or without food. No titration required.
• Chronic Kidney Disease:
• 10 mg orally once daily. Continue even if eGFR declines, unless contraindicated.

Elderly:

• No dose adjustment solely based on age. Monitor renal function regularly.

Pediatrics:

• Safety and efficacy not established in individuals under 18 years.

Renal Impairment:

• eGFR ≥ 30 mL/min/1.73 m²: Initiate or continue therapy.
• eGFR < 30 mL/min/1.73 m²: Not recommended for glycemic control in T2DM; may continue for heart failure or CKD indications.
• Discontinue if dialysis is initiated.

Hepatic Impairment:

• Mild/moderate: No adjustment needed.
• Severe: Use with caution due to limited data.

Route of Administration:

• Oral, once daily in the morning.

Empagliflozin is a selective inhibitor of sodium-glucose co-transporter 2 (SGLT2) located in the proximal renal tubules. By blocking SGLT2, it reduces glucose reabsorption in the kidneys, increasing urinary glucose excretion. This leads to reduced plasma glucose levels, modest weight loss, and blood pressure reduction. Additionally, in heart failure and CKD, its benefits are thought to result from improved cardiac preload/afterload, reduced intraglomerular pressure, and beneficial metabolic and hemodynamic effects that are independent of glucose lowering.

• Absorption:
  Oral bioavailability approximately 78%. Peak plasma concentrations (Tmax) reached within 1.5–2 hours.
• Distribution:
  Volume of distribution (Vd): ~73.8 L. Highly protein-bound (>86%).
• Metabolism:
  Primarily metabolized via glucuronidation (UGT2B7, UGT1A3, UGT1A8, UGT1A9). Minimal CYP450 metabolism.
• Elimination:
• Half-life: ~12.4 hours (allows once-daily dosing)
• Excretion: ~54% via feces (mainly unchanged), ~41% via urine (mainly metabolites)

• Pregnancy:
  Empagliflozin is not recommended during the second and third trimesters due to potential risk to fetal renal development. No adequate human data. Use only if the potential benefit justifies the potential risk.
• Lactation:
  It is unknown whether Empagliflozin is excreted in human milk. Due to the potential for serious adverse effects in breastfed infants, breastfeeding is not recommended during treatment.
• General Recommendation:
  Avoid use during pregnancy and lactation unless absolutely necessary. Alternative therapies preferred.

• Primary Class: Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitor
• Subclass: Antihyperglycemic agent with cardiovascular and renal benefits

• Known hypersensitivity to Empagliflozin or any component of the formulation
• Severe renal impairment (eGFR <30 mL/min/1.73 m²) for glycemic control indication
• Patients on dialysis
• Diabetic ketoacidosis (DKA), including euglycemic DKA

• Ketoacidosis (including euglycemic DKA): Can occur even with normal blood glucose; monitor for nausea, vomiting, abdominal pain.
• Volume depletion: Risk of hypotension, especially in elderly or patients on diuretics.
• Genital mycotic infections: Higher incidence in both males and females.
• Fournier’s gangrene: Rare but serious; requires immediate medical attention.
• Acute kidney injury: Monitor renal function, especially with NSAIDs or diuretics.
• Bone fractures: Increased risk reported in some studies.
• Hypoglycemia: Risk increased when used with insulin or sulfonylureas.
• Lower limb amputation: Though more associated with canagliflozin, caution is advised in patients with peripheral vascular disease or neuropathy.

Common Side Effects:

• Genitourinary:
• Female genital mycotic infections
• Urinary tract infections
• Increased urination
• Metabolic:
• Hypoglycemia (when combined with insulin or sulfonylurea)
• Increased thirst
• Cardiovascular:
• Hypotension (due to volume depletion)
• Gastrointestinal:
• Nausea
• Constipation

Serious Adverse Effects:

• Diabetic ketoacidosis (including euglycemic)
• Fournier’s gangrene
• Acute kidney injury
• Hypovolemia and dehydration
• Hypersensitivity reactions (rash, angioedema)

• Diuretics (e.g., furosemide): Increased risk of dehydration and hypotension
• Insulin and insulin secretagogues: Increased risk of hypoglycemia
• RAAS inhibitors (e.g., ACE inhibitors, ARBs): Enhanced hypotensive effects
• Lithium: SGLT2 inhibitors may increase lithium clearance
• CYP450: Minimal interaction as Empagliflozin is not significantly metabolized via CYP enzymes
• Alcohol: Increases risk of ketoacidosis

• Updated CKD Indication (FDA & EMA):
  Empagliflozin is now approved for slowing CKD progression even in non-diabetic patients.
• Heart Failure Guidelines (ESC, AHA):
  Empagliflozin is strongly recommended in HFrEF patients regardless of diabetes status (Class I recommendation).
• KDIGO 2024:
  Empagliflozin included as first-line therapy in CKD patients to reduce progression and cardiovascular risk.

• Temperature: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C–30°C.
• Humidity: Protect from excessive moisture.
• Light: Store in original packaging to protect from light.
• Handling: No reconstitution required. Do not freeze. Keep out of reach of children.