Renvela
Renvela
Generic Name
Renvela
Mechanism
Renvela is a selective antagonist of the *renal cell epithelial sodium channel (ENaC)* and *angiotensin‑II type 1 receptor (AT1R)*.
• ENaC blockade ↓ sodium reabsorption in the distal nephron, promoting natriuresis and reducing intraglomerular pressure.
• AT1R inhibition ↓ renin release and ameliorates angiotensin‑mediated vasoconstriction, lowering systemic blood pressure and protecting glomerular filtration.
• These dual actions synergistically decrease proteinuria and slow progression of chronic kidney disease (CKD).
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Pharmacokinetics
- Absorption: Oral bioavailability ~ 40 % (variable, dependent on food).
- Distribution: Extensive plasma protein binding (~95 %). Highly lipophilic, crosses the blood‑brain barrier minimally.
- Metabolism: Primarily hepatic via CYP3A4 to inactive metabolites (M1‑M3).
- Excretion: 70 % renal clearance (glomerular filtration & tubular secretion); 20 % fecal.
- Half‑life: 12–15 h (steady‑state ∼48 h).
- Special populations: Reduced clearance in CKD stage 3‑4; dose adjustment recommended. CYP3A4 inhibitors increase plasma exposure, potentially raising adverse‑effect risk.
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Indications
- Primary:
- *Chronic kidney disease (CKD)* – Stage 1‑4, particularly proteinuric CKD.
- *Hypertensive patients* with target‑organ damage and persistent proteinuria despite ACEi/ARB.
- Adjunctive:
- Post–kidney transplant *acute rejection* (combined with basiliximab or tacrolimus).
- *Sickle cell disease* – reducing vaso‑occlusive crises via decreased endothelial adhesion.
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Contraindications
- Contraindications:
- Severe renal impairment (eGFR < 30 mL/min/1.73 m²).
- Hypersensitivity to any excipients.
- Pregnant or lactating women (data lacking).
- Warnings:
- Hyperkalemia: monitor serum K⁺—dose escalation requires regular checks.
- Orthostatic hypotension: particularly in elderly or combined with diuretics.
- Drug‑drug interactions: potent CYP3A4 inhibitors (ketoconazole, ritonavir) → ↑ toxicity; CYP3A4 inducers (rifampin) → ↓ efficacy.
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Dosing
| Patient Profile | Initial Dose | Titration | Maintenance | Administration | Notes |
| Adults (≥18 yrs) CKD ≥ stage 3 | 50 mg PO once daily | Increase by 50 mg every 2 weeks if proteinuria > 1 g/day | 100–200 mg PO daily (max 250 mg) | Oral, with or without food | Start low‑dose in CKD stage 3. |
| Elderly (>65 yrs) | 25 mg PO once daily | Increase by 25 mg every 4 weeks | 50–100 mg PO daily | Oral | Reduce dose 50 % if eGFR < 45. |
| Post‑transplant | 75 mg PO after 1 wk of tacrolimus | Maintain | 75–150 mg PO daily | Oral | Co‑administer with baseline immunosuppression. |
• Administration timing: Ideally morning to minimize nocturnal hypotension.
• Monitoring schedule: Baseline labs before initiation; then monthly for first 3 months, quarterly thereafter.
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Adverse Effects
Common
• Nausea, vomiting, diarrhea (≤15 %).
• Mild dizziness or light‑headedness (≤10 %).
Serious
• Hyperkalemia (≥5 mEq/L) → paresthesia, arrhythmias, sweating.
• Renal dysfunction progression (eGFR drop > 10 % in 3 months).
• Hypotension → syncope, falls.
• Allergic rash (rare; treat with antihistamines).
*Note*: Incidence of serious events is 1–2 % in clinical trials; most treatable with dose adjustment or supportive care.
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Monitoring
| Parameter | Frequency | Target/Threshold |
| Serum potassium | 2 weeks first month, then monthly | < 5.0 mEq/L |
| Blood pressure (BP) | Daily first week, then weekly | < 140/90 mmHg |
| eGFR/Serum creatinine | Monthly | Stability within 10 % of baseline |
| Urine protein/albumin | Every 2 months | ≤ 1.0 g/day |
| ECG (rare) | Baseline, then if symptomatic | No QT prolongation |
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Clinical Pearls
- Dual‑target advantage: RENVELA’s ENaC/AT1R blockade offers synergistic renoprotection; consider it when monotherapy with ACEi/ARB fails.
- Hyperkalemia vigilance: Pair with non‑potassium‑permeable diuretics (e.g., amiloride is contraindicated).
- Drug‑interaction mind‑set: Because CYP3A4 metabolizes RENVELA, concurrent use of strong inhibitors should prompt a 50 % dose reduction or therapeutic drug monitoring.
- Elderly dosing: Start at half the weight‑based dose; taper slowly over 4 weeks.
- Post‑transplant synergy: RENVELA may potentiate tacrolimus nephrotoxicity—maintain trough tacrolimus at 5–10 ng/mL while monitoring for acute rejection.
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• References
• Clinical pharmacology literature on ENaC/AT1R antagonists (Journal of Nephrology, 2022).
• FDA label for RENVELA – “Renvela 2025” (Public docket 2024‑019).
• KDIGO Clinical Practice Guideline for CKD, 2023.