Sacubitril

BRAND NAMES:

Entresto - contains the active ingredients sacubitril and valsartan. It is available in the form of tablets used to treat heart problems.

MECHANISM OF ACTION:

Combination is an angiotensin receptor-neorilysin inhibitor.

Sacubitril: Sacubitril's mechanism of action is as a Neprilysin inhibitor, which is responsible for the degradation of atrial and brain natriuretic peptides. The cardiovascular and renal effects of sacubitril's active metabolite in heart failure are attributed to increased levels of peptides degraded by neprilysin, increased urine cGMP, and decreased plasma MR-proANP and NT-BNP.

Valsartan: The Mechanism of Action of Valsartan It is an angiotensin II receptor type 1 inhibitor that lowers blood pressure while blocking the vasoconstrictor and aldosterone-secreting properties of angiotensin II.

PHARMACOKINETICS:

ABSORPTION: Sacubitril's peak plasma concentration occurs within 0.5 to 2 hours of oral absorption. Food has no clinical effect on sacubitril's systemic exposure, while valsartan's peak plasma concentration lasts 1.5 hours.

DISTRIBUTION: The mean apparent volume of distribution of sacubitril is 103L and Valsartan 75L.

METABOLISM: Sacubtril is converted to LBQ657 via esterase. Valsartan is barely metabolised. A low concentration of a hydroxyl metabolite was detected in plasma.

EXCRETION: Sacubitril is excreted through urine in 52–68% and 37–48% in faeces.

Valsartan is excreted through urine in 13% and excreted 86% through faeces.

PHARMACODYNAMICS:

Sacubitril with valsartan administration resulted in a significant non-sustained increase in natriuresis, increased urine cGMP, and decreased plasma MR-proANP and NT-proBNP as compared to valsartan. In HFrEF patients, it dramatically boosted urine ANP and cGMP and plasma cGMP while decreasing plasma NT-proBNP, aldosterone, and endothelin-1. This combination had no effect on the QTC interval.

DOSAGE AND ADMINISTRATION:

The combination of valsartan and sacubtril is available as a tablet, which are little beads of medication that can be sprinkled over meals and taken orally. The tablets are often taken twice a day, with or without food. Sprinkle pills are mixed into meals and consumed twice a day.
Sacubitril and Valsartan pills are available in the strengths of 24 mg/26 mg, 49 mg/51 mg, and 97 mg/103 mg.

DRUG INTERACTIONS:

Drug interaction of sacubitril may include

• Antihypertensive: aliskiren, spironolactone
• Anti-arrhythmic: sotalol
• Pain killers—aspirin
• Lipid-lowering agent: rosuvastatin, atorvastatin
• Anti-diabetics: insulin glargine and insulin detemir
• Blood thinner—heparin

CONTRAINDICATIONS:

Drugs that directly affect the renin-angiotensin system, such as sacubitril-valsartan, can harm or kill the developing foetus. When a pregnancy is confirmed, cease sacubitril-valsartan as soon as possible. Hypersensitivity to any component or a history of angioedema due to previous ACE inhibitor or ARB medication. The combination of neprilysin inhibitors and ACE inhibitors may increase the risk of angioedema; do not take an ACE inhibitor within 36 hours after switching to or from sacubitril and valsartan.

SIDE EFFECTS:

Common side effects of valsartan and sacubitril

• Cough
• tiredness

Serious side effects of valsartan and sacubitril

• Rash
• Itching
• Difficulty breathing

OVERDOSE:

Symptoms of overdose may include

• Dizziness
• fainting

TOXICITY:

Sacubitril-valsartan is unlikely to be eliminated by hemolysis. The most common adverse events are hypotension, hyperkalaemia, cough, dizziness, and renal failure.