Generic Name

Farxiga (dapagliflozin)

Mechanism

• SGLT2 blockade in proximal renal tubules:
• Inhibits glucose reabsorption via luminal SGLT2 → ↑ urinary glucose excretion → ↓ post‑prandial and fasting plasma glucose.
• Reduces intraglomerular pressure by counteracting tubuloglomerular feedback → renoprotective effect.
• Lowers plasma volume (natriuresis) → modest decrease in preload/afterload → benefits in HFrEF/HFpEF.
• Metabolic shift towards ketogenesis: transient rise in ketone bodies, important safety point in monitoring for ketoacidosis.

Pharmacokinetics

• Absorption:
• Oral bioavailability ≈ 70%–90%; Tmax 2–4 h.
• Dose‑linear up to 25 mg once daily.
• Distribution:
• Protein binding ≈ _10%_.
• Volume of distribution ≈ 250 L.
• Metabolism & Excretion:
• Minimal hepatic metabolism (UGT1A9 glucuronidation).
• 83 % excreted unchanged in urine; 17 % via feces/other routes.
• Half‑life: 12–15 h (pharmacodynamic effect persists longer).
• Renal clearance: Decreases with CKD (e.g., GFR < 30 mL/min/1.73 m²).

Indications

1. Type 2 diabetes mellitus (T2DM)
• Adjunct or add‑on to diet/exercise or other antidiabetic agents.

2. Heart failure (HF)
• HFrEF and HFpEF with LVEF > 40 %—reduces hospitalization for HF and cardiovascular death.

3. Chronic kidney disease (CKD)
• CKD stages 2‑4 (GFR ≥ 30 mL/min/1.73 m²) to slow eGFR decline.

4. Cardioprotective therapy
• In patients with T2DM + HF or CKD for dual glucose‑lowering & organ‑protective effects.

Contraindications

• Contraindicated in type 1 diabetes (risks ketoacidosis).
• CRF stage 4–5 (eGFR < 15 mL/min/1.73 m²) & dialysis (efficacy ↓, risk ↑).
• Hypotension or volume‑depleted patients – monitor for orthostatic changes.
• Active genital or urinary tract infection – may worsen.
• Pregnancy – category D; avoid exposure.
• Uncontrolled type 2 diabetes with severe hyperglycaemia – monitor glucose closely (risk of hypoglycaemia with concomitant agents).

Dosing

| CKD (Stages 2–4) | 5 mg PO once daily | Maintain 5 mg | 5 mg | CrCl < 60 mL/min; hold if CrCl 12 h missed, delay; never double dose.

Adverse Effects

• Common (≥ 2 %):
• Genital mycotic infections (vulvovaginal in women, balanitis in men).
• Urinary tract infections (UTIs).
• Polyuria, polydipsia.
• Mild hypoglycaemia (when combined with insulin/ sulfonylureas).
• Serious (≤ 1 %):
• DKA (diabetic ketoacidosis) – early signs: nausea, vomiting, abdominal pain, Kussmaul respirations.
• Hypotension/ syncope – due to osmotic diuresis.
• Acute kidney injury (volume depletion).
• Fournier’s gangrene (rare).
• Fractures & amputations (reported in some trials but uncertain causal link).

Monitoring

Clinical Pearls

• “SGLT2 = Sodium‑Glucose Transporter‑2”: The drug exploits the kidney’s counter‑regulatory mechanism; it lowers glucose *and* mildly lowers blood pressure simultaneously—ideal for diabetic patients with hypertension.
• “Renal‑Kidney–Heart Nexus”: Farxiga’s dual benefit in CKD and HF underscores the interconnectedness of the glomerular filtration rate and cardiac preload‑afterload; treat both simultaneously.
• “Tolerability Window”: Initiate at 5 mg for CKD or patients at higher risk of volume depletion; 10 mg soon after stable eGFR >30 mL/min—reduces AEs while maintaining efficacy.
• “Bio‑Pump Cascade”: Even after dose is titrated down–especially in CKD, a 25 mg dose still blocks >90 % SGLT2 due to reduced renal clearance—over dosing beyond 25 mg yields diminishing return.
• “Keto‑Scope”: Patients on dapagliflozin and ketone‑overproducing diets (e.g., very‑low‑carb) need pre‑emptive ketone monitoring to avoid silent DKA—a critical counseling point.
• “Hypotension Hidden”: Early in therapy, patients may experience orthostatic hypotension; advise standing slowly and monitoring BP at outpatient visits.

Bottom line for clinicians: Farxiga is a versatile SGLT2 inhibitor that improves glycaemic control, offers cardio‑renal protection, and should be integrated with comprehensive monitoring to mitigate its unique adverse event profile.