sacubitril

Action and Spectrum

Actions and spectrum: 

sacubitril is a neprilysin inhibitor. It works by inhibiting the enzyme neprilysin, which is responsible for breaking down certain substances in the body, including natriuretic peptides.

By inhibiting neprilysin, sacubitril increases the levels of natriuretic peptides, like atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP). These peptides help to relax blood vessels and remove sodium and water from the body, which can reduce workload on heart and improve heart failure symptoms. 

Drug Interaction

Adverse Reaction

Frequency not defined 

Fatigue 

Orthostatic Hypotension 

Anemia 

Renal Impairment 

Weakness 

Dizziness 

Vertigo 

Increased serum Potassium Level 

Black Box Warning

Black Box Warning: 

There is no specific black box warning for sacubitril. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

History of angioedema: Patients who’ve experienced angioedema with these medications in the past should avoid sacubitril/valsartan. 

Pregnancy: sacubitril/valsartan is contraindicated during pregnancy due to potential fetal harm. 

Renal Impairment: The severe renal impairment may require dosage adjustments, as sacubitril/valsartan can affect kidney function. 

Hypotension: sacubitril/valsartan can cause low blood pressure, particularly after the initial dose. Patients at risk of hypotension should be carefully monitored, and dose adjustments may be necessary.

Caution: 

• Hyperkalemia: sacubitril/valsartan can lead to increased levels of potassium in the blood. Regular monitoring of potassium levels is essential, especially in patients at risk of hyperkalemia. 
• Dual Blockade: The concomitant use of ACE inhibitors, angiotensin II receptor blockers (ARBs), or aliskiren is not recommended, as it may increase the risk of hypotension, renal dysfunction, and hyperkalemia. 
• Symptomatic Hypotension: Patients should be advised to report symptoms of low blood pressure promptly, such as dizziness or lightheadedness. 
• Elderly: Use caution in elderly patients, as they may be more susceptible to hypotension.

Comorbidities: 

• Hypertension: It can contribute to the development of heart failure and often coexists with heart failure. sacubitril/valsartan includes valsartan, which is an angiotensin II receptor blocker (ARB) used to manage high blood pressure. 
• Coronary Artery Disease (CAD): Coronary artery disease, often resulting from atherosclerosis, can lead to heart failure. sacubitril/valsartan can help manage heart failure in these cases. 
• Diabetes: Diabetes is common in people with heart failure. Managing blood glucose levels is essential in such cases. 
• Chronic Kidney Disease (CKD): Kidney dysfunction is common in heart failure patients. sacubitril/valsartan may require dose adjustments in patients with renal impairment. 
• Chronic Obstructive Pulmonary Disease (COPD): COPD can coexist with heart failure and requires careful management, considering the impact of medications on the respiratory system. 

Pregnancy / Lactation

Pregnancy consideration: pregnancy category: not assigned 

Lactation: excreted into human milk: unknown  

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.   
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

sacubitril is a neprilysin inhibitor that works by inhibiting the enzyme neprilysin, which breaks down various substances, including natriuretic peptides that help regulate blood vessels and fluid balance. By inhibiting neprilysin, sacubitril increases the levels of natriuretic peptides, promoting vasodilation and diuresis, ultimately reducing the workload on the heart.

This mechanism of action makes sacubitril particularly beneficial in managing heart failure by improving cardiac function and reducing the risk of adverse events. sacubitril is often administered in combination with valsartan as sacubitril/valsartan to enhance its therapeutic effects.  

Pharmacodynamics: 

• Increased natriuretic peptides: sacubitril inhibits the breakdown of natriuretic peptides. These peptides promote vasodilation, reduce sodium reabsorption, and increase diuresis, leading to decreased blood volume and lower blood pressure. 
• Vasodilation: By inhibiting neprilysin, sacubitril increases the levels of natriuretic peptides, which relax blood vessels, resulting in vasodilation. This effect helps reduce the workload on the heart and improve cardiac function. 
• Reduced aldosterone levels: Natriuretic peptides also inhibit the secretion of aldosterone, a hormone that promotes salt and water retention. By reducing aldosterone levels, sacubitril further contributes to diuresis and fluid balance. 
• Improved cardiac remodelling: sacubitril’s actions lead to favorable cardiac remodeling in patients with heart failure. It can help mitigate pathological changes in the heart structure and function seen in heart failure with reduced ejection fraction (HFrEF). 
• Symptomatic relief: Patients with heart failure may experience symptomatic relief, including reduced dyspnea and improved exercise tolerance. 

Pharmacokinetics: 

Absorption 

sacubitril is orally administered in the form of sacubitril sodium. It is well absorbed from the gastrointestinal tract. 

Distribution 

sacubitril is bound to plasma proteins to a significant extent, primarily to albumin. It has a relatively large volume of distribution, indicating that it distributes widely in the body. 

Metabolism 

sacubitril is a prodrug, which means it needs to be metabolized to its active form in the body. It is primarily metabolized by esterases in the liver to form sacubitrilat, its active metabolite. 

Elimination and excretion 

sacubitrilat, the active metabolite, is eliminated via the kidneys. Both sacubitril and sacubitrilat have a short elimination half-life. The metabolites are excreted in the urine. 

Adminstartion

Administration: 

• Dosage: The recommended dose will be determined by your healthcare provider. It’s important to follow their instructions and the dosing information provided with the medication. 
• Timing: sacubitril is typically taken once or twice daily. The exact timing and frequency will be specified by your healthcare provider. 
• With or Without Food: sacubitril can be taken with or without food. However, it is commonly recommended to take it without food to optimize absorption. 
• Consistency: Try to take the medication at the same time(s) each day to maintain a consistent level of the drug in your system. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: sacubitril 

Pronounced: (sa-KYOO-bi-tril)  

Why do we use sacubitril? 

sacubitril is primarily indicated for the treatment of heart failure with reduced ejection fraction (HFrEF). Its use is to reduce the risk of hospitalization and cardiovascular death in patients with this condition. sacubitril works as a neprilysin inhibitor, which helps reduce the strain on the heart and improve its function. It’s an important component of heart failure management for eligible patients.