Sacubitril and Valsartan 97 mg; 103 mg Tablet, 60-count
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Angiotensin II receptor blockers (ARBs), other combinations class.
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🩺 Clinical
The combination of valsartan and sacubitril is usually used in combination with other medications to lower the risk of death and hospitalization in adults with certain types of heart failure. The combination of valsartan and sacubitril is also used to treat certain types of heart failure in children 1 year of age and older. Valsartan is in a class of medications called angiotensin II receptor antagonists. It works by blocking the action of certain natural substances that tighten the blood vessels, allowing the blood to flow more smoothly and the heart to pump more efficiently. Sacubitril is in...
Read the full MedlinePlus article ↗- Sacubitril and valsartan works on two fronts at once. One part (sacubitril) helps your body's own protective heart hormones stick around longer, which helps your kidneys get rid of...
- What exactly is this medication supposed to do for my heart failure?
- That's a really important question. A few combinations need to be avoided or watched carefully. You should never take this with an ACE inhibitor like lisinopril or enalapril at the...
- Can I take it with my other medications? I'm also on ibuprofen sometimes for pain.
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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UNII OP1R32D61U
Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
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UNII 68401960MK
Crospovidone is a synthetic polymer made from polyvinylpyrrolidone. It acts as a disintegrant, helping tablets break apart quickly in the stomach so the medicine dissolves and absorbs into the body.
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UNII 2165RE0K14
A plant-based thickener made from cellulose that helps control how quickly the medicine dissolves and releases its active ingredient. It also binds ingredients together and improves the tablet's texture and handling during manufacturing.
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UNII 70097M6I30
Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
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UNII 3WJQ0SDW1A
Polyethylene glycol is a synthetic liquid or solid polymer used in medicines as a solvent, lubricant, and humectant. It helps dissolve active ingredients, reduces friction during manufacturing, and retains moisture in the final product.
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UNII 532B59J990
Polyvinyl alcohol is a synthetic polymer made from plant-derived materials. It's used as a binder to hold ingredients together, a film-former in coatings, and a thickener in liquid formulations.
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UNII ETJ7Z6XBU4
Silicon dioxide is a naturally occurring mineral used as a glidant and anti-caking agent. It helps powder ingredients flow smoothly and prevents clumping during manufacturing and storage.
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UNII 7SEV7J4R1U
A powder made from a naturally occurring mineral. In medicines, talc works as a glidant and anti-caking agent, helping tablets and capsules flow smoothly during manufacturing and preventing clumping.
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UNII 15FIX9V2JP
Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
9 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · Q2 2026 | $1.45 | $87.14 / 60 tablets |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Sacubitril and Valsartan 97 mg/1; 103 mg 00904-7581-04 | Major | 1 tablet | $0.593 | AB | Availability likely | — |
| Sacubitril and valsartan 97 mg/1; 103 mg 31722-0675-18 | Camber | 180 tablets | $0.593 | AB | Availability likely | — |
| Sacubitril and Valsartan 97 mg/1; 103 mg 33342-0572-09 | Macleods | 60 tablets | $0.593 | AB | Availability likely | — |
| Sacubitril and Valsartan Sacubitril and Valsartan 97 mg/1; 103 mg 43598-0645-18 | Dr. | 180 tablets | $0.593 | AB | Availability likely | — |
| Sacubitril and Valsartan 97 mg/1; 103 mg 50268-0608-13 | AvPAK | 1 tablet | $0.593 | AB | Availability likely | — |
| Sacubitril and Valsartan 97 mg/1; 103 mg 60687-0977-57 | American | 1 tablet | $0.593 | AB | Availability likely | — |
| Sacubitril and Valsartan 97 mg/1; 103 mg 69238-2733-01 | Amneal | 60 tablets | $0.593 | AB | Availability likely | — |
| sacubitril and valsartan 97 mg/1; 103 mg 70748-0197-07 | Lupin | 60 tablets | $0.593 | AB | Availability likely | — |
| Sacubitril and Valsartan 97 mg/1; 103 mg 70954-0977-20 | ANI | 60 tablets | $0.593 | AB | Availability likely | — |
| Sacubitril and Valsartan 97 mg/1; 103 mg 72205-0282-18 | Novadoz | 180 tablets | $0.593 | AB | Availability likely | — |
| Sacubitril and Valsartan 97 mg/1; 103 mg 82293-0029-10 | Novugen | 60 tablets | $0.593 | AB | Availability likely | — |
| Entresto 97 mg/1; 103 mg 00078-0696-20 | Novartis | 60 tablets | $11.592 | AB | Availability likely | — |
| sacubitril and valsartan 97 mg/1; 103 mg 13668-0636-05 | Torrent | 500 tablets | — | AB | FDA listed | — |
| sacubitril and valsartan 97 mg/1; 103 mg 13668-0747-05 | Torrent | 500 tablets | — | AB | FDA listed | — |
| Sacubitril and Valsartan 97 mg/1; 103 mg 42385-0932-18 | Laurus | 180 tablets | — | AB | FDA listed | — |
| sacubitril and valsartan 97 mg/1; 103 mg 46708-0558-10 | Alembic | 10 tablets | — | AB | FDA listed | — |
| sacubitril and valsartan 97 mg/1; 103 mg 51407-0937-10 | Golden | 1000 tablets | — | AB | FDA listed | — |
| sacubitril and valsartan 97 mg/1; 103 mg 62332-0558-10 | Alembic | 10 tablets | — | AB | FDA listed | — |
| Sacubitril and Valsartan 97 mg/1; 103 mg 67877-0709-51 | Ascend | 180 tablets | — | AB | FDA listed | — |
| Sacubitril and Valsartan 97 mg/1; 103 mg 67877-0950-33 | Ascend | 10 tablets | — | AB | FDA listed | — |
| Sacubitril and Valsartan 97 mg/1; 103 mg 70069-0855-60 | Somerset | 60 tablets | — | AB | FDA listed | — |
| Sacubitril and Valsartan 97 mg/1; 103 mg 70377-0033-11 | Biocon | 30 tablets | — | AB | FDA listed | — |
| sacubitril and valsartan 97 mg/1; 103 mg 70710-1274-04 | Zydus | 100 tablets | — | AB | FDA listed | — |
| sacubitril and valsartan 97 mg/1; 103 mg 70771-1923-04 | Zydus | 100 tablets | — | AB | FDA listed | — |
| Entresto 97 mg/1; 103 mg 71610-0807-37 | Aphena | 3120 tablets | — | AB | FDA listed | — |
| Sacubitril and Valsartan 97 mg/1; 103 mg 71610-0955-19 | Aphena | 3060 tablets | — | AB | FDA listed | — |
| Sacubitril and Valsartan 97 mg/1; 103 mg 71610-0984-37 | Aphena | 3120 tablets | — | AB | FDA listed | — |
| Sacubitril and Valsartan 97 mg/1; 103 mgthis 72865-0312-60 | XLCare | 60 tablets | — | AB | FDA listed | — |
| Sacubitril and Valsartan 97 mg/1; 103 mg 73190-0007-10 | AvKARE | 1000 tablets | — | AB | FDA listed | — |
| Sacubitril and Valsartan 97 mg/1; 103 mg 73190-0019-18 | AvKARE | 180 tablets | — | AB | FDA listed | — |
| Sacubitril and Valsartan 97 mg/1; 103 mg 82293-0040-10 | Novugen | 60 tablets | — | AB | FDA listed | — |
| Sacubitril and Valsartan 97 mg/1; 103 mg 72603-0882-01 | NorthStar | 60 tablets | — | AB | FDA listed | — |
| Sacubitril and Valsartan 97 mg/1; 103 mg 60290-0087-01 | Umedica | 60 tablets | — | AB | FDA listed | — |
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⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 72865-0312-10 | 1000 TABLET in 1 BOTTLE (72865-312-10) | 2026-04-01 | Active |
| 72865-0312-18 | 180 TABLET in 1 BOTTLE (72865-312-18) | 2025-09-30 | Active |
| 72865-0312-60 You're viewing this | 60 TABLET in 1 BOTTLE (72865-312-60) | 2025-09-30 | Active |
You're viewing the smallest of 3 pack sizes for this product.
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| NDC identity (package / product / labeler codes) | ✓ Available |
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| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
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| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
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📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: FETAL TOXICITY • When pregnancy is detected, discontinue Sacubitril and Valsartan Tablets as soon as possible. (5.1) • Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. (5.1) WARNING: FETAL TOXICITY See full prescribing information for complete boxed warning . • When pregnancy is detected, discontinue sacubitril and valsartan tablets as soon as possible.
(5.1) • Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. (5.1)
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Sacubitril and valsartan tablets are a combination of sacubitril, a neprilisin inhibitor, and valsartan, an angiotensin II receptor blocker, and sacubitril and valsartan tablets are indicated: • to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure. Benefits are most clearly evident in patients with left ventricular ejection fraction (LVEF) below normal. ( 1.1 ) • for the treatment of symptomatic heart failure with systemic left ventricular systolic dysfunction in pediatric patients aged one year and older.
Sacubitril and valsartan reduces NT-proBNP and is expected to improve cardiovascular outcomes. ( 1.2 )
1.1Adult Heart Failure Sacubitril and valsartan tablets are indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure. Benefits are most clearly evident in patients with left ventricular ejection fraction (LVEF) below normal. LVEF is a variable measure, so use clinical judgment in deciding whom to treat [ see Clinical Studies ( 14.1 )] .
1.2Pediatric Heart Failure Sacubitril and valsartan tablets are indicated for the treatment of symptomatic heart failure with systemic left ventricular systolic dysfunction in pediatric patients aged one year and older. Sacubitril and valsartan tablets reduces NT-proBNP and is expected to improve cardiovascular outcomes.
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION • The recommended starting dosage for adults is 49 mg/51 mg orally twice daily. The target maintenance dose is 97 mg/103 mg orally twice daily. ( 2.2 ) • Adjust adult doses every 2 to 4 weeks to the target maintenance dose, as tolerated by the patient.
( 2.2 ) • For pediatric patients, see the Full Prescribing Information for recommended dosage, titrations, preparation and administration instructions. ( 2.3 , 2.4 ) • Reduce starting dose to half the usually recommended starting dosage for: o patients not currently taking an angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB) or previously taking a low dose of these agents. ( 2.6 ) o patients with severe renal impairment.
( 2.7 ) o patients with moderate hepatic impairment. ( 2.8 )
2.1General Considerations Sacubitril and valsartan tablets are contraindicated with concomitant use of an angiotensin-converting enzyme (ACE) inhibitor. If switching from an ACE inhibitor to sacubitril and valsartan tablets allow a washout period of 36 hours between administration of the two drugs [see Contraindications ( 4 ) and Drug Interactions ( 7.1 )].
2.2Adult Heart Failure The recommended starting dose of sacubitril and valsartan tablets are 49/51 mg orally twice-daily. Double the dose of sacubitril and valsartan tablets after 2 to 4 weeks to the target maintenance dose of 97/103 mg twice daily, as tolerated by the patient.
2.3Pediatric Heart Failure For the recommended dosage for pediatric patients aged 1 year and older, refer to Table 1 if using the tablets. Take the recommended dose orally twice daily. Adjust pediatric patient doses every 2 weeks, as tolerated by the patient.
Table 1: Recommended Dose and Titration for Pediatric Patients Using Tablets Weight (kg) Titration Step Dose (twice daily) Starting Second Final Less than 40 kg † 1.6 mg/kg 2.3 mg/kg 3.1 mg/kg At least 40 kg, less than 50 kg 24 mg/26 mg 49 mg/51 mg 72 mg/78 mg ‡ At least 50 kg 49 mg/51 mg 72 mg/78 mg ‡ 97 mg/103 mg † Use of the oral suspension is recommended in these patients. Recommended mg/kg doses are of the combined amount of both sacubitril and valsartan [see Dosage and Administration ( 2.4 )] . ‡ Doses of 72 mg/78 mg can be achieved using three 24 mg/26 mg tablets [see Dosage Forms and Strengths ( 3 )].
2.4Preparation of Oral Suspension Using Tablets Sacubitril and valsartan oral suspension can be substituted at the recommended tablet dosage in patients unable to swallow tablets. Sacubitril and valsartan 800 mg/200 mL oral suspension can be prepared in a concentration of 4 mg/mL (sacubitril/valsartan 1.96/2.04 mg/mL). Use sacubitril and valsartan 49/51 mg tablets in the preparation of the suspension.
To make an 800 mg/200 mL (4 mg/mL) oral suspension, transfer eight tablets of sacubitril and valsartan 49/51 mg film-coated tablets into a mortar. Crush the tablets into a fine powder using a pestle. Add 60 mL of Ora-Plus ® into the mortar and triturate gently with pestle for 10 minutes, to form a uniform suspension.
Add 140 mL of Ora-Sweet ® SF into mortar and triturate with pestle for another 10 minutes, to form a uniform suspension. Transfer the entire contents from the mortar into a clean 200 mL amber colored PET or glass bottle. Place a press-in bottle adapter and close the bottle with a child resistant cap.
The oral suspension can be stored for up to 15 days. Do not store above 25°C (77°F) and do not refrigerate. Shake before each use. *Ora-Sweet SF ® and Ora-Plus ® are registered trademarks of Paddock Laboratories, Inc.
2.6Dose Adjustment for Patients Not Taking an ACE inhibitor or ARB or Previously Taking Low Doses of These Agents In patients not currently taking an ACE inhibitor or an angiotensin II receptor blocker (ARB) and for patients previously taking low doses of these agents, start sacubitril and valsartan tablets at half the usually recommended starting dose. After initiation, increase the dose every 2 to 4 weeks in adults and every…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Sacubitril and valsartan tablets are supplied as oval shaped, bioconvex, film-coated tablets in the following strengths: Sacubitril and valsartan tablets 24 mg/26 mg, (sacubitril 24 mg and valsartan 26 mg) are white to off-white and debossed with “J13” on one side and “Plain” on the other side. Sacubitril and valsartan tablets 49 mg/51 mg, (sacubitril 49 mg and valsartan 51 mg) are light pink and debossed with “J14” on one side and “Plain” on the other side. Sacubitril and valsartan tablets 97 mg/103 mg, (sacubitril 97 mg and valsartan 103 mg) are white to off-white and debossed with “J15” on one side and “Plain” on the other side.
Film-coated tablets: 24/26 mg; 49/51 mg; 97/103 mg ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS Sacubitril and valsartan tablets are contraindicated: • in patients with hypersensitivity to any component • in patients with a history of angioedema related to previous ACE inhibitor or ARB therapy [see Warnings and Precautions ( 5.2 )] • with concomitant use of ACE inhibitors. Do not administer within 36 hours of switching from or to an ACE inhibitor [see Drug Interactions ( 7.1 )] • with concomitant use of aliskiren in patients with diabetes [see Drug Interactions ( 7.1 )] Hypersensitivity to any component.
( 4 ) History of angioedema related to previous ACEi or ARB therapy. ( 4 ) Concomitant use with ACE inhibitors. ( 4 , 7.1 ) Concomitant use with aliskiren in patients with diabetes.
( 4 , 7.1 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS • Observe for signs and symptoms of angioedema and hypotension. ( 5.2 , 5.3 ) • Monitor renal function and potassium in susceptible patients. ( 5.4 , 5.5 )
5.1Fetal Toxicity Sacubitril and valsartan tablets can cause fetal harm when administered to a pregnant woman. Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. When pregnancy is detected, consider alternative drug treatment and discontinue sacubitril and valsartan tablets.
However, if there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system, and if the drug is considered lifesaving for the mother, advise a pregnant woman of the potential risk to the fetus [see Use in Specific Populations ( 8.1 )].
5.2Angioedema Sacubitril and valsartan tablets may cause angioedema [see Adverse Reactions ( 6.1 )] . If angioedema occurs, discontinue sacubitril and valsartan tablets immediately, provide appropriate therapy, and monitor for airway compromise. Sacubitril and valsartan tablets must not be re-administered.
In cases of confirmed angioedema where swelling has been confined to the face and lips, the condition has generally resolved without treatment, although antihistamines have been useful in relieving symptoms. Angioedema associated with laryngeal edema may be fatal. Where there is involvement of the tongue, glottis or larynx, likely to cause airway obstruction, administer appropriate therapy, e.g., subcutaneous epinephrine/adrenaline solution 1:1000 (0.3 mL to 0.5 mL) and take measures necessary to ensure maintenance of a patent airway.
Sacubitril and valsartan tablets has been associated with a higher rate of angioedema in Black than in non-Black patients. Patients with a prior history of angioedema may be at increased risk of angioedema with sacubitril and valsartan tablets [see Adverse Reactions ( 6.1 )] . Sacubitril and valsartan tablets must not be used in patients with a known history of angioedema related to previous ACE inhibitor or ARB therapy [see Contraindications ( 4 )] .
Sacubitril and valsartan tablets should not be used in patients with hereditary angioedema.
5.3Hypotension Sacubitril and valsartan tablets lowers blood pressure and may cause symptomatic hypotension [see Adverse Reactions ( 6.1 )] . Patients with an activated renin-angiotensin system, such as volume- and/or salt-depleted patients (e.g., those being treated with high doses of diuretics), are at greater risk. Correct volume or salt depletion prior to administration of sacubitril and valsartan tablets or start at a lower dose.
If hypotension occurs, consider dose adjustment of diuretics, concomitant antihypertensive drugs, and treatment of other causes of hypotension (e.g., hypovolemia). If hypotension persists despite such measures, reduce the dosage or temporarily discontinue sacubitril and valsartan tablets. Permanent discontinuation of therapy is usually not required.
5.4Impaired Renal Function As a consequence of inhibiting the renin-angiotensin-aldosterone system (RAAS), decreases in renal function may be anticipated in susceptible individuals treated with sacubitril and valsartan tablets [see Adverse Reactions ( 6.1 )] . In patients whose renal function depends upon the activity of the renin-angiotensin-aldosterone system (e.g., patients with severe congestive heart failure), treatment with ACE inhibitors and angiotensin receptor antagonists has been associated with oliguria, progressive azotemia and, rarely, acute renal failure and death.
Closely monitor serum creatinine, and down-titrate or interrupt sacubitril and valsartan tablets in patients who develop a clinically significant decrease in renal function [see Use in Specific Populations ( 8.7 ) and Clinical Pharmacology ( 12.3 )]. As with all drugs that affect the RAAS, Sacubitril and valsartan tablets may increase blood urea and seru…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS Clinically significant adverse reactions that appear in other sections of the labeling include: • Angioedema [see Warnings and Precautions ( 5.2 )] • Hypotension [see Warnings and Precautions ( 5.3 )] • Impaired Renal Function [see Warnings and Precautions ( 5.4 )] • Hyperkalemia [see Warnings and Precautions ( 5.5 )] Adverse reactions occurring greater than or equal to 5% are hypotension, hyperkalemia, cough, dizziness, and renal failure. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact XLCare Pharmaceuticals, Inc. at 1-866-495-1995 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. A total of 6,622 heart failure patients were treated with sacubitril and valsartan in the PARADIGM-HF (vs. enalapril) and PARAGON-HF (vs. valsartan) clinical trials. Of these, 5,085 were exposed for at least 1 year.
Adult Heart Failure In PARADIGM-HF, patients were required to complete sequential enalapril and sacubitril and valsartan tablets run-in periods of (median) 15 and 29 days, respectively, prior to entering the randomized double-blind period comparing sacubitril and valsartan tablets and enalapril. During the enalapril run-in period, 1,102 patients (10.5%) were permanently discontinued from the study, 5.6% because of an adverse event, most commonly renal dysfunction (1.7%), hyperkalemia (1.7%) and hypotension (1.4%). During the sacubitril and valsartan tablets run-in period, an additional 10.4% of patients permanently discontinued treatment, 5.9% because of an adverse event, most commonly renal dysfunction (1.8%), hypotension (1.7%) and hyperkalemia (1.3%).
Because of this run-in design, the adverse reaction rates described below are lower than expected in practice. In the double-blind period, safety was evaluated in 4,203 patients treated with sacubitril and valsartan tablets and 4,229 treated with enalapril. In PARADIGM-HF, patients randomized to sacubitril and valsartan tablets received treatment for up to 4.3 years, with a median duration of exposure of 24 months; 3,271 patients were treated for more than one year.
Discontinuation of therapy because of an adverse event during the double-blind period occurred in 450 (10.7%) of sacubitril and valsartan tablets-treated patients and 516 (12.2%) of patients receiving enalapril. Adverse reactions occurring at an incidence of greater than or equal to 5% in patients who were treated with sacubitril and valsartan tablets in the double-blind period of PARADIGM-HF are shown in Table 3. In PARADIGM-HF, the incidence of angioedema was 0.1% in both the enalapril and sacubitril and valsartan tablets run-in periods.
In the double-blind period, the incidence of angioedema was higher in patients treated with sacubitril and valsartan tablets than enalapril (0.5% and 0.2%, respectively). The incidence of angioedema in Black patients was 2.4% with sacubitril and valsartan tablets and 0.5% with enalapril [see Warnings and Precautions ( 5.2 )] . Orthostasis was reported in 2.1% of patients treated with sacubitril and valsartan compared to 1.1% of patients treated with enalapril during the double-blind period of PARADIGM-HF.
Falls were reported in 1.9% of patients treated with sacubitril and valsartan tablets compared to 1.3% of patients treated with enalapril. Table 3: Adverse Reactions Reported in greater than or equal to 5% of Patients Treated with Sacubitril and valsartan tablets in the Double-Blind Period of PARADIGM-HF Sacubitril and valsartan tablets (n = 4,203) % Enalapril (n = 4,229) % Hypotension 18 12 Hyperkalemia 12 14 Cough 9 13 Dizziness 6 5 Renal failure/acute renal failure 5 5 In PARAGON-HF, no new adverse reactions were identified.
Pediatric Heart Failure The adverse reactions…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS • Avoid concomitant use with aliskiren in patients with estimated glomerular filtration rate (eGFR) less than 60. ( 7.1 ) • Potassium-sparing diuretics: May lead to increased serum potassium. ( 7.2 ) • Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): May lead to increased risk of renal impairment. ( 7.3 ) • Lithium: Increased risk of lithium toxicity. ( 7.4 )
7.1Dual Blockade of the Renin-Angiotensin-Aldosterone System Concomitant use of sacubitril and valsartan tablets with an ACE inhibitor is contraindicated because of the increased risk of angioedema [see Contraindications ( 4 )] . Avoid use of sacubitril and valsartan tablets with an ARB, because sacubitril and valsartan tablets contains the angiotensin II receptor blocker valsartan. The concomitant use of sacubitril and valsartan tablets with aliskiren is contraindicated in patients with diabetes [see Contraindications ( 4 )] .
Avoid use with aliskiren in patients with renal impairment (eGFR less than 60 mL/min/1.73 m²).
7.2Potassium-Sparing Diuretics As with other drugs that block angiotensin II or its effects, concomitant use of potassium-sparing diuretics (e.g., spironolactone, triamterene, amiloride), potassium supplements, or salt substitutes containing potassium may lead to increases in serum potassium [see Warnings and Precautions ( 5.5 )].
7.3Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) Including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors) In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, concomitant use of NSAIDs, including COX-2 inhibitors, with sacubitril and valsartan tablets may result in worsening of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically.
7.4Lithium Increases in serum lithium concentrations and lithium toxicity have been reported during concomitant administration of lithium with angiotensin II receptor antagonists. Monitor serum lithium levels during concomitant use with sacubitril and valsartan tablets.
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS • Lactation: Breastfeeding not recommended. ( 8.2 ) • Severe Hepatic Impairment: Use not recommended. ( 2.8 , 8.6 )
8.1Pregnancy Risk Summary Sacubitril and valsartan tablets can cause fetal harm when administered to a pregnant woman. Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death (see Clinical Considerations ). Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents.
In animal reproduction studies, Sacubitril and valsartan tablets treatment during organogenesis resulted in increased embryo-fetal lethality in rats and rabbits and teratogenicity in rabbits (see Data) . When pregnancy is detected, consider alternative drug treatment and discontinue sacubitril and valsartan tablets. However, if there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system, and if the drug is considered lifesaving for the mother, advise a pregnant woman of the potential risk to the fetus.
The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Clinical Considerations Fetal/Neonatal Adverse Reactions Oligohydramnios in pregnant women who use drugs affecting the renin-angiotensin system in the second and third trimesters of pregnancy can result in the following: reduced fetal renal function leading to anuria and renal failure, fetal lung hypoplasia, skeletal deformations, including skull hypoplasia, hypotension, and death. Perform serial ultrasound examinations to assess the intra-amniotic environment. Fetal testing may be appropriate, based on the week of gestation.
Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. If oligohydramnios is observed, consider alternative drug treatment. Closely observe neonates with histories of in utero exposure to sacubitril and valsartan tablets for hypotension, oliguria, and hyperkalemia.
In neonates with a history of in utero exposure to sacubitril and valsartan tablets, if oliguria or hypotension occurs, support blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and replacing renal function. Data Animal Data Sacubitril and valsartan tablets treatment during organogenesis resulted in increased embryo-fetal lethality in rats at doses greater than or equal to 49 mg sacubitril/51 mg valsartan/kg/day (less than or equal to 0.06 [LBQ657, the active metabolite] and 0.72 [valsartan]-fold the maximum recommended human dose [MRHD] of 97/103 mg twice-daily on the basis of the area under the plasma drug concentration-time curve [AUC]) and rabbits at doses greater than or equal to 5 mg sacubitril/5 mg valsartan/kg/day (2-fold and 0.03-fold the MRHD on the basis of valsartan and LBQ657 AUC, respectively).
Sacubitril and valsartan tablets is teratogenic based on a low incidence of fetal hydrocephaly, associated with maternally toxic doses, which was observed in rabbits at an sacubitril and valsartan tablets dose of greater than or equal to 5 mg sacubitril/5 mg valsartan/kg/day. The adverse embryo-fetal effects of sacubitril and valsartan tablets are attributed to the angiotensin receptor antagonist activity. Pre-and postnatal development studies in rats at sacubitril doses up to 750 mg/kg/day (2.2-fold the MRHD on the basis of LBQ657 AUC) and valsartan at doses up to 600 mg/kg/day (0.86-fold the…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Sacubitril and valsartan tablets can cause fetal harm when administered to a pregnant woman. Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death (see Clinical Considerations ). Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents.
In animal reproduction studies, Sacubitril and valsartan tablets treatment during organogenesis resulted in increased embryo-fetal lethality in rats and rabbits and teratogenicity in rabbits (see Data) . When pregnancy is detected, consider alternative drug treatment and discontinue sacubitril and valsartan tablets. However, if there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system, and if the drug is considered lifesaving for the mother, advise a pregnant woman of the potential risk to the fetus.
The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Clinical Considerations Fetal/Neonatal Adverse Reactions Oligohydramnios in pregnant women who use drugs affecting the renin-angiotensin system in the second and third trimesters of pregnancy can result in the following: reduced fetal renal function leading to anuria and renal failure, fetal lung hypoplasia, skeletal deformations, including skull hypoplasia, hypotension, and death. Perform serial ultrasound examinations to assess the intra-amniotic environment. Fetal testing may be appropriate, based on the week of gestation.
Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. If oligohydramnios is observed, consider alternative drug treatment. Closely observe neonates with histories of in utero exposure to sacubitril and valsartan tablets for hypotension, oliguria, and hyperkalemia.
In neonates with a history of in utero exposure to sacubitril and valsartan tablets, if oliguria or hypotension occurs, support blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and replacing renal function. Data Animal Data Sacubitril and valsartan tablets treatment during organogenesis resulted in increased embryo-fetal lethality in rats at doses greater than or equal to 49 mg sacubitril/51 mg valsartan/kg/day (less than or equal to 0.06 [LBQ657, the active metabolite] and 0.72 [valsartan]-fold the maximum recommended human dose [MRHD] of 97/103 mg twice-daily on the basis of the area under the plasma drug concentration-time curve [AUC]) and rabbits at doses greater than or equal to 5 mg sacubitril/5 mg valsartan/kg/day (2-fold and 0.03-fold the MRHD on the basis of valsartan and LBQ657 AUC, respectively).
Sacubitril and valsartan tablets is teratogenic based on a low incidence of fetal hydrocephaly, associated with maternally toxic doses, which was observed in rabbits at an sacubitril and valsartan tablets dose of greater than or equal to 5 mg sacubitril/5 mg valsartan/kg/day. The adverse embryo-fetal effects of sacubitril and valsartan tablets are attributed to the angiotensin receptor antagonist activity. Pre-and postnatal development studies in rats at sacubitril doses up to 750 mg/kg/day (2.2-fold the MRHD on the basis of LBQ657 AUC) and valsartan at doses up to 600 mg/kg/day (0.86-fold the MRHD on the basis of AUC) indicate that treatment with sacubitril and valsartan tablets during organogenesis, gestation and lactation may affect p…
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of sacubitril and valsartan tablets have been established for the treatment of heart failure in pediatric patients 1 year to less than 18 years. Use of sacubitril and valsartan tablets was evaluated in a multinational, randomized, double-blind trial comparing sacubitril and valsartan tablets and enalapril in 375 patients aged 1 month to less than 18 years (sacubitril and valsartan tablets n = 187; Enalapril n = 188) (PANORAMA-HF) [see Clinical Studies ( 14.2 )]. The safety profile in pediatric patients (1 year to less than 18 years) receiving sacubitril and valsartan tablets was similar to that seen in adult patients.
Limited safety and efficacy data in patients aged 1 month to less than 1 year were inadequate to support conclusions on safety and efficacy in this age group. Juvenile Animal Toxicity Data Sacubitril given orally to juvenile rats from postnatal day (PND) 7 to PND 35 or PND 70 (an age approximately equivalent to neonatal through pre-pubertal development or adulthood in humans) at doses greater than or equal to 400 mg/kg/day (approximately 2-fold the AUC exposure to the active metabolite of sacubitril, LBQ657, at an sacubitril and valsartan tablets pediatric clinical dose of 3.1 mg/kg twice daily) resulted in decreases in body weight, bone length, and bone mass.
The decrease in body weight was transient from PND 10 to PND 20 and the effects for most bone parameters were reversible after treatment stopped. Exposure at the No-Observed-Adverse-Effect-Level (NOAEL) of 100 mg/kg/day was approximately 0.5-fold the AUC exposure to LBQ657 at the 3.1 mg/kg twice daily dose of sacubitril and valsartan tablets.The mechanism underlying bone effects in rats and the translatability to pediatric patients are unknown. Valsartan given orally to juvenile rats from PND 7 to PND 70 (an age approximately equivalent to neonatal through adulthood in humans) produced persistent, irreversible kidney damage at all dose levels.
Exposure at the lowest tested dose of 1 mg/kg/day was approximately 0.2-fold the exposure at 3.1 mg/kg twice daily dose of sacubitril and valsartan tablets based on AUC. These kidney effects in neonatal rats represent expected exaggerated pharmacological effects that are observed if rats are treated during the first 13 days of life. This period coincides with 36 weeks of gestation in humans, which could occasionally extend up to 44 weeks after conception in humans.
In humans, nephrogenesis is thought to be complete around birth; however, maturation of other aspects of kidney function (such as glomerular filtration and tubular function) may continue until approximately 2 years of age. It is unknown whether post-natal use of valsartan before maturation of renal function is complete has long-term deleterious effects on the kidney.
🧓 Geriatric Use ▾
8.5Geriatric Use There were 4,143 and 3,971 heart failure patients 65 years of age and older in PARADIGM-HF and PARAGON-HF, respectively [see Clinical Studies (14)]. Of the total number of sacubitril and valsartan tablets-treated patients, 2,087 (49.6%) and 1,995 (82.9%) were 65 years of age and older, while 786 (18.7%) and 1,100 (45.7%) were 75 years of age and older in PARADIGM-HF and PARAGON-HF, respectively. No overall differences in safety or effectiveness of sacubitril and valsartan tablets have been observed between patients 65 years of age and older and younger adult patients in either study.
No relevant pharmacokinetic differences have been observed in elderly (≥65 years) or very elderly (≥75 years) patients compared to the overall population [see Clinical Pharmacology ( 12.3 )] .
🆘 Overdosage ▾
10 OVERDOSAGE Limited data are available with regard to overdosage in human subjects with sacubitril and valsartan tablets. In healthy volunteers, a single dose of sacubitril and valsartan tablets 583 mg sacubitril/617 mg valsartan, and multiple doses of 437 mg sacubitril/463 mg valsartan (14 days) have been studied and were well tolerated. Hypotension is the most likely result of overdosage due to the blood pressure lowering effects of sacubitril and valsartan tablets.
Symptomatic treatment should be provided. Sacubitril and valsartan tablets is unlikely to be removed by hemodialysis because of high protein binding.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Sacubitril and valsartan tablets contains a neprilysin inhibitor, sacubitril, and an angiotensin receptor blocker, valsartan. Sacubitril and valsartan tablets inhibits neprilysin (neutral endopeptidase; NEP) via LBQ657, the active metabolite of the prodrug sacubitril, and blocks the angiotensin II type-1 (AT 1 ) receptor via valsartan. The cardiovascular and renal effects of sacubitril and valsartan tablets in heart failure patients are attributed to the increased levels of peptides that are degraded by neprilysin, such as natriuretic peptides, by LBQ657, and the simultaneous inhibition of the effects of angiotensin II by valsartan.
Valsartan inhibits the effects of angiotensin II by selectively blocking the AT 1 receptor, and also inhibits angiotensin II-dependent aldosterone release.
12.2Pharmacodynamics The pharmacodynamic effects of sacubitril and valsartan tablets were evaluated after single and multiple dose administrations in healthy subjects and in patients with heart failure, and are consistent with simultaneous neprilysin inhibition and renin-angiotensin system blockade. In a 7-day valsartan-controlled study in patients with reduced ejection fraction (HFrEF), administration of sacubitril and valsartan tablets resulted in a significant non-sustained increase in natriuresis, increased urine cGMP, and decreased plasma MR-proANP and NT-proBNP compared to valsartan.
In a 21-day study in HFrEF patients, Sacubitril and valsartan tablets significantly increased urine ANP and cGMP and plasma cGMP, and decreased plasma NT-proBNP, aldosterone and endothelin-1. Sacubitril and valsartan tablets also blocked the AT1-receptor as evidenced by increased plasma renin activity and plasma renin concentrations. In PARADIGM-HF, Sacubitril and valsartan tablets decreased plasma NTproBNP (not a neprilysin substrate) and increased plasma BNP (a neprilysin substrate) and urine cGMP compared with enalapril.
In PARAMOUNT, a randomized, double-blind, 36-week study in patients with heart failure with LVEF greater than or equal to 45% comparing 97/103 mg of sacubitril and valsartan (n=149) to 160 mg of valsartan (n =152) twice-daily, sacubitril and valsartan decreased NT-proBNP by 17% while valsartan increased NT-proBNP by 8% at Week 12 (p = 0.005). In PARAGON-HF, sacubitril and valsartan decreased NT-proBNP by 24% (Week 16) and 19% (Week 48) compared to 6% and 3% reductions on valsartan, respectively. In PANORAMA-HF, a reduction in NT-proBNP was observed at Weeks 4 and 12 for sacubitril and valsartan tablets (40% and 50%) compared to baseline.
The NT-proBNP levels continued to decrease over the duration of the study with a reduction of 65% for sacubitril and valsartan tablets at Week 52 compared to baseline. QT Prolongation: In a thorough QTc clinical study in healthy male subjects, single doses of sacubitril and valsartan tablets 194 mg sacubitril/206 mg valsartan and 583 mg sacubitril/617 mg valsartan had no effect on cardiac repolarization. Amyloid-β: Neprilysin is one of multiple enzymes involved in the clearance of amyloid-β (Aβ) from the brain and cerebrospinal fluid (CSF).
Administration of sacubitril and valsartan tablets 194 mg sacubitril/206 mg valsartan once-daily for 2 weeks to healthy subjects was associated with an increase in CSF Aβ 1-38 compared to placebo; there were no changes in concentrations of CSF Aβ 1-40 or CSF Aβ 1-42 . The clinical relevance of this finding is unknown [see Nonclinical Toxicology ( 13 )] . Blood Pressure: Addition of a 50 mg single dose of sildenafil to sacubitril and valsartan tablets at steady state (194 mg sacubitril/206 mg valsartan once daily for 5 days) in patients with hypertension was associated with additional blood pressure (BP) reduction (approximately 5/4 mmHg, systolic/diastolic BP) compared to administration of sacubitril and valsartan tablets alone.
Co-administration of sacubitril and valsartan tablets did not significantly alter the BP effe…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Sacubitril and valsartan tablets contains a neprilysin inhibitor, sacubitril, and an angiotensin receptor blocker, valsartan. Sacubitril and valsartan tablets inhibits neprilysin (neutral endopeptidase; NEP) via LBQ657, the active metabolite of the prodrug sacubitril, and blocks the angiotensin II type-1 (AT 1 ) receptor via valsartan. The cardiovascular and renal effects of sacubitril and valsartan tablets in heart failure patients are attributed to the increased levels of peptides that are degraded by neprilysin, such as natriuretic peptides, by LBQ657, and the simultaneous inhibition of the effects of angiotensin II by valsartan.
Valsartan inhibits the effects of angiotensin II by selectively blocking the AT 1 receptor, and also inhibits angiotensin II-dependent aldosterone release.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING Sacubitril and valsartan tablets (sacubitril/valsartan) is available as unscored, ovaloid, biconvex, film-coated tablets, containing 24 mg of sacubitril and 26 mg of valsartan; 49 mg of sacubitril and 51 mg of valsartan; and 97 mg of sacubitril and 103 mg of valsartan. All strengths are packaged in bottles as described below. Tablet Color Debossment NDC # 72865-XXX-XX Sacubitril/Valsartan Bottle of 60 Bottle of 180 Bottle of 1000 24 mg/26 mg White to off-white J13 310-60 310-18 310-10 49 mg/51 mg Light pink J14 311-60 311-18 311-10 97 mg/103 mg White to off-white J15 312-60 312-18 312-10 Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature].
Protect from moisture.
📋 Description ▾
11 DESCRIPTION Sacubitril and valsartan tablets is a combination of a neprilysin inhibitor and an angiotensin II receptor blocker. Sacubitril and valsartan contains a complex comprised of anionic forms of Sacubitril, Valsartan and sodium cations in the ratio of 1:1:3, respectively. Following oral administration, the complex dissociates into sacubitril (which is further metabolized to LBQ657) and valsartan.
The complex is chemically described as Trisodium (4-{[(1S,3R)-1-([1,1´-biphenyl]-4-ylmethyl)-4-ethoxy-3-methyl-4-oxobutyl]amino}-4oxobutanoate) (N-pentanoyl-N-{[2´-(1H-tetrazol-1-id-5-yl)[1,1´-biphenyl]-4-yl]methyl}-L-valinate). Its empirical formula is C 48 H 55 N 6 O 8 .Na 3 . Its molecular mass is 913 g/mol and its schematic structural formula is: Sacubitril and Valsartan tablets are available as film-coated tablets for oral administration, containing 24 mg of sacubitril and 26 mg of valsartan; 49 mg of sacubitril and 51 mg of valsartan; and 97 mg of sacubitril and 103 mg of valsartan.
The tablet inactive ingredients are microcrystalline cellulose, low-substituted hydroxypropylcellulose, colloidal silicon dioxide, magnesium stearate, crospovidone. The film-coat inactive ingredients are polyvinyl alcohol-part hydrolised, titanium dioxide, Macrogol 4000, talc. The film-coat for the 49 mg of sacubitril and 51 mg of valsartan tablet contains iron oxide yellow and iron oxide red.
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💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise patients to read the FDA-approved patient labeling (Patient Information). Pregnancy: Advise female patients of childbearing age about the consequences of exposure to sacubitril and valsartan tablets during pregnancy. Discuss treatment options with women planning to become pregnant.
Ask patients to report pregnancies to their physicians as soon as possible [see Warnings and Precautions ( 5.1 ) and Use in Specific Populations ( 8.1 )] . Lactation : Advise patients that breastfeeding is not recommended during treatment with sacubitril and valsartan tablets [see Use in Specific Populations ( 8.2 )]. Angioedema: Advise patients to discontinue use of their previous ACE inhibitor or ARB.
Advise patients to allow a 36-hour wash-out period if switching from or to an ACE inhibitor [see Contraindications ( 4 ) and Warnings and Precautions ( 5.2 )] . Medication Guide available at https://www.xlcarepharma.com/medication-guides Manufactured for : XLCare Pharmaceuticals, Inc. 242 South Culver Street, Suite 202, Lawrenceville, GA 30046.
Manufactured by: Evaric Pharmaceuticals Inc. 155 Commerce Drive, Hauppauge, New York 11788, United States (USA) For more information, call 1-866-495-1995. Revised: 04/2026