Kerendia
Kerendia
Generic Name
Kerendia
Mechanism
Kerendia (finerenone) is a non‑steroidal mineralocorticoid receptor antagonist (MRA).
* Selective binding to the mineralocorticoid receptor (MR) with nanomolar affinity, blocking aldosterone‑mediated transcription.
* Does not possess the pro‑hormone activity of steroidal MRAs, yielding reduced fibrotic and inflammatory signaling in the kidney and heart.
* Exhibits a balanced distribution across glomerular and tubular compartments, thereby attenuating sodium‑water retention, interstitial fibrosis, and glomerular hypertrophy.
Pharmacokinetics
| Parameter | Typical Value (Adults) | Notes |
| Absorption | Rapid, peak plasma concentration (tₘₐₓ) ~1–2 h after oral dosing. | Food does not significantly alter bioavailability. |
| Distribution | Volume of distribution ≈ 0.6 L/kg; moderate plasma protein binding (~34%). | Crosses the blood‑brain barrier minimally. |
| Metabolism | Primarily hepatic via CYP3A4 (≈50 %) and *minor* CYP2D6 pathways. | N‑oxide metabolite exerts negligible activity. |
| Elimination | ~35 % renal excretion unchanged; remainder via bile/ feces. | Half‑life 7–10 h; steady state ~1 week. |
| Special Populations | In CKD stage 3–4, dose adjustment required to prevent hyperkalemia. | Limited data in severe hepatic impairment; cautious use. |
Indications
| Indication | Dose | Notes |
| Progressive chronic kidney disease (CKD) with type 2 diabetes (eGFR 25–90 mL/min/1.73 m²) | Initial 12.5 mg QD once daily; titrate to 25 mg QD after ≥4 weeks if no hyperkalemia | Adjunct to renin‑angiotensin‑system blockade (ACEi/ARB). |
| CKD without diabetes but with albuminuria and hypertension (rare, off‑label) | Similar dosing | Requires careful monitoring. |
Contraindications
* Absolute contraindication: Serum potassium >5.5 mmol/L, or active hyperkalemia.
* Relative: Severe CKD (eGFR <25 mL/min/1.73 m²) or uncontrolled hypertension.
* Warnings:
• Hyperkalemia – routine serum potassium checks every 2–4 weeks during first 6 months.
• Renal Dysfunction – monitor eGFR; dose reduce to 12.5 mg QD or discontinue if eGFR <25 mL/min/1.73 m².
• Drug Interactions – strong CYP3A4 inhibitors (e.g., ketoconazole) elevate finerenone levels; reduce dose.
• Pregnancy – Category C; avoid in pregnancy.
• Pediatric – not approved; data insufficient.
Dosing
- Start: 12.5 mg PO once daily (preferably morning).
- Titrate: Increase to 25 mg QD after ≥4 weeks if serum K⁺ ≤5.0 mmol/L and eGFR remains stable.
- Administration: With or without food; aim for same time each day to minimize variability.
- Re‑dosing: If dose is missed, take as soon as remembered, but skip the following dose to avoid double‑dosing.
Adverse Effects
| Symptom | Frequency | Management |
| Hyperkalemia | ~6–10 % | Potassium‑binding resins, reduce dietary K⁺, dose adjustment. |
| Renal insufficiency | 30 % rise in serum creatinine. | |
| Nausea, vomiting | <5 % | Take with food; antiemetics if needed. |
| Headache, dizziness | <5 % | Hydration, monitor blood pressure. |
| Serious – Sudden kidney injury or severe hyperkalemia | <1 % | Immediate evaluation, stop drug, treat hyperkalemia. |
Monitoring
| Parameter | Timing | Desired Range |
| Serum potassium | Baseline, 2‑4 weeks, then every 2–4 weeks for first 6 months, quarterly thereafter | 3.5–5.0 mmol/L |
| eGFR / Serum creatinine | Baseline, 4 weeks, then every 2–4 weeks for 6 months, quarterly | No >30 % rise in creatinine |
| Blood pressure | At each visit | <130/80 mmHg |
| Urine albumin/creatinine ratio | Baseline, 4 weeks, then every 3 months | Trending downward is desired |
| Adverse effect review | Each visit | Hyperkalemia, GI symptoms, dizziness |
Clinical Pearls
- Early Titration Trumps Delay: Initiating the 12.5‑mg dose with a short “loading window” and titrating to 25 mg QD after ensuring K⁺ stability maximizes renoprotection while keeping hyperkalemia risk manageable.
- Synergistic ACEi/ARB: Finerenone’s benefit is amplified when paired with a renin‑angiotensin‑system blocker; ensure both are titrated to target dose before adding Kerendia.
- Potassium‑Bound Resins as Adjuncts: Low‑potassium‑binding resins (e.g., patiromer) can be safely co‑administered, allowing patients whose baseline K⁺ is borderline to stay on full dosage.
- Avoiding Interference: Strong CYP3A4 inhibitors should not be co‑administered; if unavoidable, consider dose reduction and closer monitoring.
- Pregnancy Precautions: Even though data are limited, avoid prescribing Kerendia to pregnant patients; advise contraception for women of childbearing potential.
- Real‑World Data Snapshot: Post‑marketing registries note that CKD patients ≥60 % had slowed eGFR decline (~35 % relative risk reduction) when Kerendia was added to standard therapy.
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