Sacubitril-Valsartan (Sacubitril / Valsartan (Angiotensin Receptor-Neprilysin Inhibitor — ARNi))
Also sold as: Vymada, Sacuval, Entresto
Pregnancy
Cat D
Lactation
Avoid
Schedule
H
Forms
Tablet 24mg/26mg (sacubitril/valsartan — "50mg") +3
Indications
- Heart failure with reduced ejection fraction (HFrEF, EF ≤40%) — Class I indication (superior to enalapril in PARADIGM-HF)
- Heart failure with mildly reduced ejection fraction (HFmrEF, EF 41–49%) — consider in symptomatic patients
- Hypertension (off-label in some regions)
Adult Dosing
Heart failure with reduced ejection fraction (HFrEF)
Start 24/26 mg twice daily; target 97/103 mg twice daily
Start 24/26mg BD; double dose every 2–4 weeks if tolerated; target dose 97/103mg BD (highest tolerated dose)
MUST wash out ACE inhibitor for minimum 36 hours before first dose (angioedema risk). If switching from ARB, can start without washout. Check BP and renal function at each dose increase. In de novo HF or with SBP <100, start at 24/26mg BD.
Hypertension (off-label)
24/26–97/103 mg twice daily
Titrate based on BP response over 4–8 weeks
Not approved in India for hypertension; primarily used for HFrEF
Renal Dose Adjustment
| CrCl / eGFR | Dose Adjustment |
|---|---|
| eGFR ≥30 mL/min/1.73m² (mild to moderate CKD) | No dose adjustment required; monitor renal function and potassium closely |
| eGFR <30 mL/min/1.73m² (severe CKD) | Start at 24/26mg BD (low starting dose recommended); titrate cautiously; more frequent renal and electrolyte monitoring |
| Dialysis | Use with extreme caution; insufficient data; not generally recommended |
Hepatic Adjustment
Mild (Child-Pugh A): no dose adjustment. Moderate (Child-Pugh B): start at 24/26mg BD; maximum 49/51mg BD. Severe (Child-Pugh C): CONTRAINDICATED.
Pregnancy & Lactation
Pregnancy: Category D
CONTRAINDICATED in pregnancy — the valsartan component (ARB class) causes fetal renal dysgenesis, oligohydramnios, anuria, skull hypoplasia, limb contractures, and fetal/neonatal death. Pregnancy category D (same as all ARBs and ACE inhibitors in 2nd/3rd trimester). Discontinue as soon as pregnancy detected. Use effective contraception.
Lactation: Avoid
Unknown if sacubitril/valsartan is excreted in human milk. Given the ARB component and potential for serious adverse effects in infant (renal, cardiovascular), breastfeeding should be discontinued if this drug is required.
Top Drug Interactions
| Interacting Drug | Effect | Severity |
|---|---|---|
| ACE inhibitors (ramipril, enalapril, lisinopril) | CONTRAINDICATED — concurrent use or use within 36 hours causes life-threatening angioedema (dual renin-angiotensin system blockade + neprilysin inhibition dramatically increases bradykinin levels). Must have 36-hour washout period from last ACE inhibitor dose. | Major |
| Aliskiren (direct renin inhibitor) | CONTRAINDICATED in patients with diabetes or CKD — dual RAAS blockade increases risk of hypotension, hyperkalemia, and renal failure | Major |
| Potassium-sparing diuretics (spironolactone, eplerenone) / potassium supplements | Additive hyperkalemia risk — monitor potassium closely, especially when combined with spironolactone (common in HF triple therapy) | Major |
| NSAIDs (ibuprofen, diclofenac) | Reduce antihypertensive and diuretic effect; can cause acute kidney injury (especially in elderly or dehydrated patients) | Moderate |
| Lithium | ARB component reduces lithium renal clearance — toxic lithium levels. Monitor lithium levels frequently. | Major |
| Statins (atorvastatin) | Sacubitril inhibits OATP1B1/1B3 transporters — increases atorvastatin Cmax by 2-fold and AUC by 1.3-fold. Avoid high-dose atorvastatin (>40mg); monitor for myopathy. | Moderate |
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Side Effects
Common
- Hypotension (symptomatic) — especially at initiation and dose increases
- Hyperkalemia — especially with concomitant spironolactone/eplerenone
- Renal impairment (creatinine rise)
- Dizziness
- Cough (less than ACE inhibitors — valsartan is ARB)
- Fatigue
- Headache
- Nausea
Serious / Discontinue If
- Angioedema — risk dramatically increased if used within 36 hours of ACE inhibitor; can be fatal
- Severe hypotension — especially in volume-depleted patients, elderly, those on diuretics
- Severe hyperkalemia (K+ >6.0 mEq/L) — can precipitate fatal arrhythmias
- Acute kidney injury — reversible usually; monitor creatinine and eGFR
- Fetotoxicity / teratogenicity — CONTRAINDICATED in pregnancy
Contraindications
- Concurrent ACE inhibitor use (any timing — 36-hour washout required after last ACE inhibitor dose)
- Prior history of angioedema related to ACE inhibitor or ARB
- Pregnancy (all trimesters)
- Concurrent aliskiren use in patients with diabetes or renal impairment (eGFR <60)
- Severe hepatic impairment (Child-Pugh C)
- Hypersensitivity to sacubitril or valsartan
- Bilateral renal artery stenosis (relative)
Available Indian Brands
| Brand | Manufacturer | Price (approx) |
|---|---|---|
| Vymada 50mg (24/26) | Novartis India | ₹285/10 tablets |
| Sacuval 50mg (24/26) | Sun Pharma | ₹189/10 tablets |
| Entresto 50mg (24/26) | Novartis India | ₹310/10 tablets |
Monitoring Required
- Blood pressure — at each visit; especially after dose increases; target SBP 100–130 mmHg in HF
- Serum potassium — before initiation, at 1–2 weeks, after each dose increase, then every 3–6 months; target K+ <5.5 mEq/L
- Serum creatinine and eGFR — before initiation, at 1–2 weeks, after each dose increase, then every 3–6 months; acceptable up to 30% creatinine rise if stable
- Serum sodium — hyponatremia in HF can worsen with RAAS blockade
- BNP / NT-proBNP — every 3–6 months in HF to assess treatment response
- Echocardiography — ejection fraction at 3–6 monthly intervals during optimization
- Symptoms of angioedema — facial/tongue/laryngeal swelling (stop drug and emergency treatment if occurs)
- Pregnancy test before initiation in women of childbearing age
- Lithium levels if co-prescribed
- NYHA class and 6-minute walk test — functional improvement assessment
Patient Counseling Points
- CRITICAL: If you have been taking a ramipril, enalapril, lisinopril or other "pril" tablet, you must stop it for at least 36 hours before starting this medicine — failure to do so can cause life-threatening facial/throat swelling
- Report immediately if you notice swelling of face, lips, tongue, or throat — this is a medical emergency (angioedema)
- You may feel dizzy when standing up initially — stand up slowly; take the tablet at the same time daily
- Monitor your blood pressure at home — inform doctor if consistently below 90/60
- Avoid potassium supplements or salt substitutes (contain potassium) without doctor approval
- Avoid NSAIDs like ibuprofen, diclofenac — use paracetamol for pain instead
- Women of childbearing age must use reliable contraception — drug is harmful to the fetus
- Report any reduction in urination or swelling of legs (kidney concerns)
- Regular blood tests (kidney function, potassium) are mandatory — do not skip
- This medicine is significantly better than older heart failure drugs — it reduces your risk of hospitalization by ~20%. Take it consistently.
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Clinically reviewed by: Dr. Priya Menon, DM (Cardiology), PGIMER Chandigarh
Last reviewed: 2026-04-01
References
- Drugs.com — Sacubitril/Valsartan Monograph
- CIMS India — Sacubitril Valsartan
- PARADIGM-HF Trial (McMurray et al., NEJM 2014)
- ACC/AHA Heart Failure Guidelines 2022
- ESC Heart Failure Guidelines 2021
- Indian Heart Failure Guidelines 2022 (CSI)
- Indian National Formulary 2023
- Micromedex — Sacubitril/Valsartan Drug Interactions