Mayzent
Mayzent®
Generic Name
Mayzent®
Mechanism
- Inhibits renal sodium‑glucose cotransporter‑2 (SGLT‑2) in the proximal tubule
- ↓ Glucose reabsorption → increased urinary glucose excretion (glucosuria)
- Indirect effects:
- ↓︎ intravascular volume through osmotic diuresis
- ↓︎ preload and afterload (decreased arterial stiffness)
- ↑︎ natriuresis and diuresis → lower systemic vascular resistance
- ↓︎ cardiomyocyte stress (reduces reactive oxygen species, improves mitochondrial efficiency)
- Net result: improved hemodynamics and reduced HF exacerbations
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Pharmacokinetics
| Parameter | Typical Findings |
| Absorption | Rapid oral absorption; peak plasma concentration ∼2 h post‑dose |
| Bioavailability | ~87 % (food reduces rate, not extent) |
| Distribution | Volume of distribution ~4 L/kg; protein binding ~30‑40 % |
| Metabolism | Primarily glucuronidation (UGT1A9, UGT2B4) → inactive metabolites |
| Elimination | Renal excretion (~80 % unchanged + metabolites); plasma half‑life ~12 h |
| Special Populations |
• Mild‑moderate renal impairment: minimal dose adjustment; avoid if CrCl < 30 ml/min due to lack of data
• Liver impairment: no dose adjustment required; no known hepatotoxicity |
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Indications
- Primary
- Treatment of HFrEF (EF ≤ 40 %) to reduce the risk of hospitalization for HF and cardiovascular death in patients with or without type 2 diabetes.
- Off‑label (pre‑FDA)
- Glycemic control in type 2 diabetes (approved under the generic name dapagliflozin).
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Contraindications
| Contraindication | Warning |
| Known hypersensitivity to dapagliflozin or any component | Severe renal impairment (CrCl < 30 ml/min) – avoid |
| Pregnant or lactating women | Risk of ketoacidosis, especially in type 1 diabetes or prolonged fasting |
| Active ketoacidosis (e.g., DKA) | Use with caution in patients with *hypovolemia* or *electrolyte* disturbances |
| History of genital mycotic infections | Monitor for genital & urinary tract infections |
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Dosing
- Initial dose: 5 mg orally once daily (preferably with a meal).
- Maintenance: Increase to 10 mg once daily if needed and tolerated; only the 5 mg or 10 mg tablets are approved for HFrEF.
- Renal function:
- CrCl ≥ 30 ml/min: start 5 mg → 10 mg as tolerated
- CrCl < 30 ml/min: avoid (clinical trials excluded these patients).
- Duration: Lifelong therapy for HF management; titrate to the maximum tolerated dose.
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Adverse Effects
| Category | Examples |
| Common | Genitourinary infections (vaginal/penile), mild hyperkalemia, dizziness, mild hypotension, decreased serum creatinine (indicates diuresis), thirst |
| Serious | Euglycemic ketoacidosis, volume depletion/orthostatic hypotension, serious genital infections, Fournier’s gangrene (rare), worsening renal function in acute illness, hypoglycemia when combined with sulfonylureas or insulin |
*Key signals:* sudden weight loss, fruity breath, abdominal pain → evaluate for ketoacidosis.
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Monitoring
- Baseline: HbA1c (if diabetic), serum creatinine and eGFR, electrolytes (K⁺, Na⁺, Cl⁻), Hb, urinalysis for ketones and glucose, BP (standing/rising).
- Follow‑up:
- Every 3–6 months: eGFR, electrolytes, weight, BP, and signs of dehydration.
- If clinically indicated: serum ketones, glucose monitoring (for patients at risk of DKA).
- Imaging: Routine echocardiogram at baseline and every 12 months to track EF changes.
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Clinical Pearls
- PEARL 1: *Mayzent* is **cardioprotective independent of glycemic control* – use it in HFrEF even if the patient’s HbA1c is <7 %.
- PEARL 2: The renal benefit is dose‑dependent but safe up to CrCl 45 ml/min; avoid when CrCl < 30 ml/min because of unstudied safety.
- PEARL 3: Combination with loop diuretics can magnify diuresis; monitor for hypotension, especially in the elderly or those with baseline low BP.
- PEARL 4: *Monitor for ketoacidosis with atypical, non‑glycemic symptoms* (fatigue, abdominal pain, fruity breath) in any patient on SGLT‑2 inhibitors, even with normal glucose.
- PEARL 5: Pregnancy counseling is crucial; switch to a lower‑risk antidiabetic agent (e.g., metformin) if pregnancy is planned.
- PEARL 6: Avoid abrupt discontinuation in acute illness—gradual tapering is preferred to prevent rehospitalization due to fluid overload.
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