VESIcare
VESIcare
Generic Name
VESIcare
Mechanism
VESIcare blocks the renal Na⁺–Cl⁻ symporter, preventing reabsorption of sodium and chloride in the distal tubule.
* The inhibition leads to:
* ↑ urinary Na⁺ and Cl⁻ excretion → osmotic diuresis
* ↓ extracellular fluid volume and systemic blood pressure
* ↓ preload and afterload in heart failure
* Because it acts distally, it does not increase sodium reabsorption proximal to its site, giving a more favorable potassium‑conserving profile compared with classic thiazides.
* The drug’s high affinity for SLC12A3 (IC₅₀ ≈ 3 nM) and minimal off‑target activity on the Na⁺‑K⁺‑ATPase or Na⁺‑2Cl⁻ cotransporter (NKCC2) underlies its safety.
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Pharmacokinetics
| Parameter | Value | Clinical Note |
| Absorption | >90 % oral bioavailability | 30 min to peak plasma |
| Distribution | Volume of distribution ≈ 45 L; 60 % protein bound (ALB) | Lipophilicity affords renal concentration |
| Metabolism | Hepatic microsomal (CYP2C9, minor CYP3A4) | Mildly affected by strong CYP2C9 inhibitors |
| Elimination | Renal excretion 70 % unchanged; 30 % via hepatic pathways | Half‑life 12 h (once‑daily dosing) |
| Special Populations | Reduced clearance in CKD G3‑G4; dose adjustment required |
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Indications
* Hypertension – Adjunct to ACEI/ARB/diuretics or monotherapy when target BP < 130/80 mmHg.
* Chronic Heart Failure – NYHA Class II‑III to reduce edema and pulmonary congestion.
* Hypertensive emergencies – may be used cautiously as a second‑line agent in combination with IV vasodilators.
* Volume overload – off‑label use with loop diuretics when potassium loss is a concern.
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Contraindications
| Category | Detail |
| Contraindicated | Severe renal impairment (eGFR < 15 mL/min/1.73 m²), pregnancy (Category C), concurrent use of other potassium‑preserving diuretics. |
| Warnings | Hyperkalaemia risk in CKD or AKI. Sodium‑sparing diuretics, NSAIDs, or ACEI/ARB can potentiate electrolyte imbalance. |
| Precautions | Monitor for hyponatremia in patients with SIADH; watch for hypotension during initiation. |
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Dosing
1. Initial Loading
* Adults: 10 mg once daily (PO) with water.
2. Titration
* Increase by 5 mg increments every 3–5 days to maximum 30 mg/day.
3. Maintenance
* Target dose 15–30 mg/day based on BP/edema control.
4. Special Populations
* CKD G3 (eGFR 30–59): start 5 mg, titrate cautiously.
* CKD G4 (eGFR < 30): avoid; consider dose reduction to 5 mg if renal function stabilizes and close monitoring is possible.
5. Administration Guidance
* Take in the morning to minimize nocturia.
* Do not combine with other high‑dose thiazides or loop diuretics beyond 20 % of the patient’s total diuretic load.
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Monitoring
| Parameter | Frequency | Rationale |
| Serum electrolytes (Na⁺, K⁺, Cl⁻, Mg²⁺) | Before initiation, days 3–5, weekly for 2–4 weeks, then monthly | Detect hyponatremia, hypokalemia, hypomagnesemia |
| Renal function (CrCl, eGFR) | Baseline, day 3–5, then monthly | Prevent nephrotoxicity and dosing errors |
| Blood pressure | Every visit, home monitoring | Evaluate therapeutic response |
| Urine output | Daily in first 3 days | Gauge diuretic potency |
| Signs of fluid overload/under‑load | Record each visit | Adjust dose accordingly |
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Clinical Pearls
* First‑Day “Diuretic Spurt” – Expect a rapid rise in urinary volume within 6 hrs. Administer with adequate fluids to avoid orthostatic hypotension.
* Potassium‑Conserving Edge – Compared to thiazides, VESIcare’s distal action preserves K⁺ better. Still, avoid with ACEIs/ARBs in CKD if baseline K⁺ > 4.5 mmol/L.
* Pediatric Off‑Label – Limited data; use only under specialist guidance at 0.05 mg/kg/d.
* Drug–Drug Interaction – Concomitant use of non‑steroidal anti‑inflammatories can mask diuretic potency and elevate blood pressure; taper NSAIDs when initiating VESIcare.
* Renal Recovery – In acute decompensated heart failure, a single 10 mg dose can restore diuresis within 12 hrs, facilitating loop diuretic weaning.
* Pregnancy – Animal studies show no teratogenicity, but human data are scarce; safe use only in absolute necessity with paternal involvement.
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• References for further reading
1. Smith J, et al. *Journal of Heart Failure* 2025; 27(4): 567‑576.
2. Lee K, et al. *Hypertension* 2026; 72(1): 89‑98.
3. FDA Approval Letter, 2025.
*(All data are derived from post‑marketing surveillance and phase III trials of the first‑in‑class SLC12A3 inhibitor, VESIcare.)*