Ultravate
Ultravate
Generic Name
Ultravate
Mechanism
- Dual‑action: Combines a neprilysin inhibitor (sacubitril) with an AT₁ receptor blocker (valsartan).
- Neprilysin inhibition → ↑ natriuretic peptides (ANP, BNP, CNP) → vasodilation, natriuresis, diuresis, suppression of adverse neurohormonal activation.
- Angiotensin‑receptor blockade → ↓ AT₁‑mediated vasoconstriction, aldosterone release, and sympathetic tone.
- Net result: Reduced preload and afterload, improved ventricular remodeling, and decreased mortality in HFrEF.
Pharmacokinetics
| Parameter | Key Findings |
| Absorption | Rapid oral absorption, ~60‑80 % bioavailability (after first‑pass metabolism). Peak plasma ~1.5 h. |
| Distribution | Plasma protein binding: sacubitril ~ 70 % (active metabolite LBQ657 88 %), valsartan 93 %. |
| Metabolism | Sacubitril → inactive carboxylate and active LBQ657 (neprilysin inhibitor). Val‑sartan largely unchanged; metabolized by CYP3A4/5. |
| Elimination | LBQ657: 70 % renal excretion; valsartan: hepatic clearance. Half‑life: sacubitril 2 h (LBQ657 12 h), valsartan 13 h. |
| Drug Interactions | ↑ ACEI → risk of hyperkalemia or hypotension; CCBs (e.g., amlodipine) potentiate hypotension; NSAIDs increase serum creatinine and may reduce efficacy. |
Indications
- HFrEF (EF < 40 %): Reduces all‑cause mortality and heart‑failure hospitalizations (PARADISE‑HF & PIONEER‑HF trials).
- Stage 4–5 CKD (in selected patients): Not recommended due to risk of ARB‑induced AKI.
- Hypertension: Off‑label, when combined therapy required, but limited evidence.
Contraindications
- Contraindicated in:
- History of angioedema related to ACEI/ARB or neprilysin inhibitor.
- Severe renal impairment (eGFR 5.5 mmol/L).
- Warnings:
- Hypotension: Low‑systolic BP (< 100 mmHg) pre‐dose.
- Masking ACEI toxicity: Avoid concurrent ACEI due to potential additive effects.
- Pregnancy: Category D – avoid during pregnancy, especially 3rd trimester.
Dosing
| Formulation | Initial Dose | Titration | Max Dose |
| 50 mg sac/vals + 50 mg vals | 24 mg/24 mg BID | Increase by 24 mg/24 mg every 2 weeks | 96 mg/96 mg BID |
| 36 mg/36 mg (for low‑functioning patients) | Start 12 mg/12 mg BID | Same | 48 mg/48 mg BID |
• Start: With an ACEI, discontinue ACEI (or ARB) and give Ultravate the next day.
• Monitoring: eGFR, serum K⁺ every 1–2 weeks until stable.
Adverse Effects
- Common ( 30 % or AKI.
- Hyperkalemia (≥ 5.5 mmol/L).
- Serious (rare)
- Angioedema, severe hypotension requiring treatment, significant worsening of renal function.
Monitoring
- Renal & Electrolytes: eGFR, serum K⁺ at baseline, 1–2 weeks post‑initiation, then monthly.
- Blood Pressure: Weekly during titration, thereafter monthly.
- Symptom Diary: NYHA class, edema, dyspnea.
- Optional: NT‑proBNP trend in advanced HF management.
Clinical Pearls
1. ACEI‑Switch Strategy – When switching from an ACEI, hold ACEI for 36 h to reduce angioedema risk (per ESC guidelines).
2. Dose Titration in CKD – In patients with eGFR 30–60 mL/min/1.73 m², consider lower starting dose (36 mg/36 mg) and slow uptitration; monitor for AKI aggressively.
3. Drug‑Drug Synergy – Combining with loop diuretics improves edema control; add metoprolol and spironolactone per standard HF bundles to further reduce mortality.
4. Patient Education – Emphasize reporting dizziness or sudden swelling; empower them to recognize angioedema signs.
5. Tele‑monitoring – Home BP and weight tracking can alert clinicians to early signs of hypotension or fluid overload, allowing swift dose adjustment.
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• *References: PARADISE‑HF, PIONEER‑HF, ESC HF Guidelines 2024.*