Product Overview
[Drug Name]
Generic Name: Sacubitril/Valsartan Sodium Tablets
Trade Name: Noxinto Sacubitril/Valsartan Sodium Tablets 200mg x 7 tablets
[Main Ingredients]
Active ingredient: Sacubitril/Valsartan Sodium Chemical Name: Octadecasodium Hexa(4-{[(1S,3R)-1-(1,1'-biphenyl)-4-ylmethyl)-4-ethoxy-3-methyl-4-oxobutyl]amino}-4-oxobutanoate)hexa(N-pentanoyl-N-{2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-L-valine)-water (1/15) Molecular Formula: C24H28NNaO5·C24H27N5Na2O3·2/ Molecular weight of H2O: 957.99
[Properties]
This product is available as a purple-white oval film-coated tablet debossed with "LZ" on one side and "NVR" on the other side (50 mg strength), or as a pale yellow oval film-coated tablet debossed with "L1" on one side and "NVR" on the other side (100 mg strength), or as a pale pink oval film-coated tablet debossed with "L11" on one side and "NVR" on the other side (200 mg strength).
[Indications/Main Functions]
1. As sacubitril/valsartan 50mg, 100mg, and 200mg: Indicated for the treatment of adult patients with chronic heart failure with reduced ejection fraction (NYHAI-IV, LVEF ≤ 40%) to reduce the risk of cardiovascular death and heart failure hospitalization. Sacubitril/valsartan sodium tablets can be used in combination with other heart failure medications, as an alternative to angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin I receptor blockers (ARBs). 2. Sacubitril/valsartan 100mg and 200mg: For the treatment of essential hypertension.
[Specifications]
200mg*7 tablets
[Dosage and Administration]
This product can be taken with or without food (see [Pharmacokinetics]). Due to the potential risk of angioedema when used with ACEIs, this product is contraindicated in combination with ACEIs. If switching from an ACEI to this product, ACEI therapy must be discontinued for at least 36 hours before starting this product (see [Contraindications]). This product has angiotensin I receptor antagonist activity and is therefore not recommended for use with ARBs (see [Precautions] and [Drug Interactions]). For chronic heart failure with reduced ejection fraction: The recommended starting dose is 100mg twice daily. For patients not currently taking ACE inhibitors or ARBs, or those taking low doses of these medications, the recommended starting dose of 50 mg twice daily is recommended. Based on patient tolerance, the dose should be doubled every 2 to 4 weeks to a target maintenance dose of 200 mg twice daily. Do not initiate 50 mg twice daily in patients with a serum potassium level >5.4 mmol/L. Caution should be exercised when initiating 50 mg twice daily in patients with a SBP <100 mmHg, and blood pressure should be monitored. For patients with a SBP ≤100 mmHg or ≤110 mmHg, a starting dose of 50 mg twice daily should be considered. If patients develop intolerance to 50 mg twice daily (systolic blood pressure ≤95 mmHg, symptomatic hypotension, hyperkalemia, or renal impairment), it is recommended to adjust concomitant medications, temporarily reduce the dose, or discontinue 50 mg twice daily (see Precautions). For essential hypertension, the recommended starting dose is 200 mg once daily. In patients whose blood pressure is not adequately controlled with 200 mg once daily, the dose can be increased to 400 mg once daily. This product can be used alone or in combination with other antihypertensive drugs other than ACE inhibitors (see [Contraindications]) and ARBs (see [Precautions]). Special Populations: Patients with renal impairment: No dose adjustment is required for patients with chronic heart failure and reduced ejection fraction with mild renal impairment (eGFR 60-90 mL/min/1.73 m²). The recommended starting dose for patients with chronic heart failure and reduced ejection fraction with moderate renal impairment (eGFR 30-60 mL/min/1.73 m²) is 50 mg twice daily. Because experience in patients with severe renal impairment (eGFR <30 mL/min/1.73 m²) is very limited, this product should be used with caution in such patients; the recommended starting dose is 50 mg twice daily. No dose adjustment is required for patients with essential hypertension with mild or moderate renal impairment (eGFR 30-90 mL/min/1.73 m²). The safety and efficacy of this drug in patients with essential hypertension and severe renal impairment (eGFR <30 mL/min/1.73 m²) have not been established. There is no experience with this drug in patients with end-stage renal disease and chronic heart failure with reduced ejection fraction or with essential hypertension, so its use is not recommended in such patients. Hepatic Impairment: No starting dose adjustment is required for patients with mild hepatic impairment (Child-Pugh class A). The recommended starting dose for patients with chronic heart failure and reduced ejection fraction with moderate hepatic impairment (Child-Pugh class B) is 50 mg twice daily. As tolerated, the dose of this drug can be doubled every 2-4 weeks to a target maintenance dose of 200 mg twice daily. The recommended starting dose for patients with essential hypertension with moderate hepatic impairment (Child-Pugh class B) is 100 mg once daily. This drug is not recommended for patients with severe hepatic impairment (Child-Pugh class C) (see [Pharmacology and Toxicology]). Elderly patients (over 65 years): No dose adjustment is required for patients over 65 years of age.
[Adverse Reactions]
See package insert for details.
[Contraindications]
This product is contraindicated in patients with hypersensitivity to the active ingredients (sacubitril, valsartan) or any of the excipients. It is contraindicated for use with ACE inhibitors (see [Precautions], [Dosage and Administration], and [Drug Interactions]). This product must be taken 36 hours after discontinuation of ACE inhibitor therapy. It is contraindicated in patients with a history of angioedema associated with ACE inhibitor or ARB therapy. It is contraindicated in patients with hereditary or idiopathic angioedema. In patients with type 2 diabetes, Entresto is contraindicated for use with aliskiren (see [Precautions] and [Drug Interactions]). It is contraindicated in patients with severe hepatic impairment, biliary cirrhosis, and cholestasis. It is contraindicated in patients during the second and third trimesters of pregnancy (see [Use in Pregnant and Lactating Women]).
[Precautions]
Warning: Embryotoxicity: This product may cause fetal harm when used by pregnant women. Use of drugs that act on the renin-angiotensin system during the second and third trimesters can reduce fetal renal function and increase fetal and neonatal morbidity and mortality. Upon discovery of pregnancy, consider alternative medications and discontinue this product. However, if there is no appropriate alternative treatment (for drugs that affect the renin-angiotensin system) and this product is considered life-saving for the mother, inform pregnant women of the potential risk to the fetus. Angioedema: Entresto may cause angioedema. During the double-blind phase of the PARADIGM-HF study, angioedema occurred in 0.5% of patients treated with Entresto and 0.2% of patients treated with enalapril (see Adverse Reactions). If angioedema occurs, immediately discontinue Entresto, administer appropriate treatment, and monitor for airway involvement. Rechallenge of Entresto is contraindicated. Confirmed cases of angioedema limited to the face and lips generally resolve without treatment, although antihistamines may help relieve symptoms. Angioedema associated with laryngeal edema can be fatal. If edema involves the tongue, glottis, or larynx, airway obstruction may occur. Administer appropriate treatment, such as subcutaneous epinephrine solution 1:1000 (0.3 mL to 0.5 mL), and take necessary measures to ensure airway patency. The incidence of angioedema is higher in Black patients compared to non-Black patients using Entresto. Patients with a prior history of angioedema may be at increased risk of angioedema when using Entresto (see Adverse Reactions). Patients with a known history of angioedema associated with ACE inhibitor or ARB therapy should not use Entresto (see Contraindications). Dual blockade of the renin-angiotensin-aldosterone system (RAAS): Due to the risk of angioedema, Entresto should not be used with ACE inhibitors. Entresto must be started 36 hours after the last dose of an ACE inhibitor. If Entresto therapy is discontinued, ACE inhibitors must be started 36 hours after the last dose of Entresto (see Contraindications, Dosage and Administration, and Drug Interactions). Entresto should be used with caution with direct renin inhibitors (such as aliskiren) (see Contraindications and Drug Interactions). Entresto is concomitantly used with aliskiren in patients with type 2 diabetes (see Contraindications). Due to its angiotensin II receptor antagonist activity, Entresto should not be used concomitantly with ARBs (see [Dosage and Administration] and [Drug Interactions]). Hypotension: Entresto may lower blood pressure and may cause symptomatic hypotension. Patients with activated renin-angiotensin system (e.g., those with volume depletion or electrolyte depletion, such as those receiving high-dose diuretics) are at greater risk. In the double-blind phase of the PARADIGM-HF study, 18% of Entresto-treated patients and 12% of enalapril-treated patients reported adverse events of hypotension (see [Adverse Reactions]), with approximately 1.5% of patients in both treatment groups reporting serious adverse events of hypotension. Correct any volume depletion or electrolyte depletion before administering Entresto or initiate treatment at a lower dose. If hypotension occurs, consider adjusting the dose of the diuretic, concomitant antihypertensive medication, and treating other causes of hypotension (e.g., volume depletion). If hypotension persists despite these measures, reduce the Entresto dose or temporarily discontinue it. Permanent discontinuation of treatment is generally not necessary. Renal Impairment: Due to inhibition of the renin-angiotensin-aldosterone system (RAAS), treatment with Entresto may predictably lead to decreased renal function in susceptible individuals. In the double-blind phase of the PARADIGM-HF study, adverse events of renal failure were reported in 5% of patients in both the Entresto and enalapril groups (see Adverse Reactions). In patients whose renal function depends on the activity of the renin-angiotensin-aldosterone system (e.g., patients with severe congestive heart failure), treatment with ACE inhibitors and ARBs may be associated with oliguria, progressive azotemia, and rarely, acute renal failure and death. If a patient develops clinically significant decreased renal function, closely monitor serum creatinine and reduce or interrupt Entresto dose (see Dosage and Administration - Specific Populations and Pharmacokinetics). As with other drugs that affect the renin-angiotensin-aldosterone system, Entresto may cause elevations in blood urea and serum creatinine in patients with bilateral or unilateral renal artery stenosis. Entresto should be used with caution in patients with renal artery stenosis, and renal function monitoring is recommended. Hyperkalemia: Through its effects on the RAAS, hyperkalemia may occur with Entresto therapy. In the double-blind phase of the PARADIGM-HF study, adverse events of hyperkalemia were reported in 12% of Entresto-treated patients and 14% of enalapril-treated patients (see Adverse Reactions). Serum potassium levels should be monitored regularly and treated appropriately, particularly in patients with risk factors for hyperkalemia (e.g., severe renal impairment, diabetes mellitus, hypoaldosteronism, or those on a high-potassium diet). Entresto dose reduction or interruption may be necessary (see Dosage and Administration). NYHA Class IV Patients: Due to limited clinical experience in NYHA Class IV patients, caution should be exercised when initiating Entresto therapy in such patients. B-type natriuretic peptide (BNP): BNP is a substrate for neprilysin. BNP is not a suitable biomarker for heart failure in patients receiving Entresto. Patients with Hepatic Impairment: Clinical experience is limited in patients with moderate hepatic impairment (Child-Pugh class B) or AST/ALT values greater than twice the upper limit of normal. Exposure may be increased in these patients, and the safety profile has not been established. Therefore, caution is advised in such patients. This product is contraindicated in patients with severe hepatic impairment, biliary cirrhosis, or cholestasis (Child-Pugh class C).
