Products
The fixed combination of the neprilysin inhibitor sacubitril with valsartan was approved in the United States, the EU, and many countries in 2015 in the form of film-coated tablets (Entresto). The combination is also referred to as LCZ696.
Structure and properties
Sacubitril (C24H29NO5, Mr = 411.5 g/mol) is an ester prodrug that is hydrolyzed in the organism by esterases to the active metabolite LBQ657. The tablets contain a complex of the negatively charged sacubitril with the negatively charged valsartan, as well as sodium ions and water in the ratio 1:1:3:2.5. After ingestion, the complex dissolves and both substances are released.
Effects
Sacubitril (ATC C09DX04) is an inhibitor of neprilysin (neutral endopeptidase, NEP). This enzyme is found in the kidney and elsewhere and inactivates endogenous natriuretic peptides. These include:
- ANP: Atrial Natriuretic Peptide
- BNP: Brain Natriuretic Peptide
- CNP: C-type Natriuretic Peptide
These peptides have diuretic, vasodilator, natriuretic, antihypertensive and antiproliferative properties. Inhibition of degradation promotes their effects.
Indications
For the treatment of systolic heart failure. To reduce the risk of cardiovascular death and morbidity.
Dosage
According to the SmPC. Tablets are taken twice daily (morning and evening), independent of meals.
Contraindications
- Hypersensitivity
- Combination with ACE inhibitors
- Angioedema in patient history, associated with ACE inhibitors or sartans.
- Combination with aliskiren in patients with diabetes mellitus or patients with impaired renal function.
- Severe renal dysfunction
- Pregnancy
Full precautions can be found in the drug label.
Adverse effects
The most common possible adverse effects of the fixed combination include low blood pressure, hyperkalemia, cough, impaired renal function, and dizziness.
